1,364 results on '"Fukayama"'
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2. 人のディジタルツイン実現への挑戦「Another Me」
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Atsushi Fukayama
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2023
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3. Estimating and Visualizing Persuasiveness of Participants in Group Discussions
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Atsushi Ito, Yukiko I. Nakano, Fumio Nihei, Tatsuya Sakato, Ryo Ishii, Atsushi Fukayama, and Takao Nakamura
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General Computer Science - Published
- 2023
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4. 血液透析導入期における栄養摂取状況と栄養状態の把握
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Akiho Yamashita, Masayuki Kaku, Mayumi Kawabata, Mika Fukayama, Yuri Yotsumoto, and Kengo Kajiwara
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Computer Networks and Communications ,Hardware and Architecture ,Software - Published
- 2023
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5. Derivation of pancreatic acinar cell carcinoma cell line <scp>HS</scp> ‐1 as a patient‐derived tumor organoid
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Daisuke Hoshi, Emiri Kita, Yoshiaki Maru, Hiroyuki Kogashi, Yuki Nakamura, Yasutoshi Tatsumi, Osamu Shimozato, Kazuyoshi Nakamura, Kentaro Sudo, Akiko Tsujimoto, Ryo Yokoyama, Atsushi Kato, Tetsuo Ushiku, Masashi Fukayama, Makiko Itami, Taketo Yamaguchi, and Yoshitaka Hippo
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Cancer Research ,Oncology ,General Medicine - Abstract
Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long-term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy-derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS-1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS-1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.
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- 2022
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6. Assessment of liver function-related mRNA expression and fluorescence imaging in outflow-obstructed regions in rats
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Daisuke Ito, Yoshikuni Kawaguchi, Yoshinori Inagaki, Kyoji Ito, Yuichiro Mihara, Junichi Kaneko, Mariko Tanaka, Masashi Fukayama, Norihiro Kokudo, and Kiyoshi Hasegawa
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Surgery ,General Medicine - Abstract
The liver function in outflow-obstructed regions is reportedly impaired; however, the functional decrease has not been quantitatively assessed. We therefore evaluated the uptake of indocyanine green (ICG) into hepatocytes and the mRNA expression associated with the liver function in outflow-obstructed regions using rat models.A total of 20 rats with the ligation of the right median hepatic vein to induce outflow obstruction were studied. Five rats each were grouped by the time of re-laparotomy, and the fluorescence intensity (FI) values of ICG. The mRNA expression, including that of Albumin, Cytochrome P450 (Cyp) 1a2, Cyp3a1, Cyp7a1, and Gamma-glutamylcysteine synthetase, in outflow-obstructed (mRNAMicroscopic fluorescence imaging showed that the FI values were significantly lower in outflow-obstructed regions than in non-outflow-obstructed regions at 12 h, 24 h, and 3 days after ligation of the hepatic vein. The mRNAThe liver function in outflow-obstructed regions was impaired in terms of the uptake of ICG and the mRNA expression. Our findings may help estimate the postoperative functional remnant liver volume by considering the decrease in the liver function in outflow-obstructed regions.
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- 2022
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7. Characterization of the Functions of Starch Synthase IIIb Expressed in the Vegetative Organs of Rice (Oryza sativaL.)
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Ryutaro Morita, Naoko Crofts, Satoko Miura, Ken-ichi Ikeda, Naohiro Aoki, Hiroshi Fukayama, and Naoko Fujita
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Physiology ,Cell Biology ,Plant Science ,General Medicine - Abstract
Rice is the model C3 crop for investigating the starch biosynthesis mechanism in endosperm because of its importance in grain production. However, little is known about starch biosynthesis in the vegetative organs of rice. In this study, we used novel rice mutants by inserting Tos17 into the starch synthase (SS) IIIb gene, which is mainly expressed in the leaf sheath (LS) and leaf blade (LB), and an ss1 mutant to clarify the differences in roles among SS isozymes during starch biosynthesis. Native polyacrylamide gel electrophoresis (PAGE)/activity staining for SS, using LS and LB of ss mutants, revealed that the lowest migrating SS activity bands on the gel were derived from SSIIIb activity and those of two ss3b mutants were not detected. The apparent amylose content of LS starch of ss3b mutants increased. Moreover, the chain-length distribution and size-exclusion chromatography analysis using ss mutants showed that SSIIIb and SSI synthesize the B2–B3 chain and A–B1 chain of amylopectin in the LS and LB respectively. Interestingly, we also found that starch contents were decreased in the LS and LB of ss3b mutants, although SSI deficiency did not affect the starch levels. All these results indicated that SSIIIb synthesizes the long chain of amylopectin in the LS and LB similar to SSIIIa in the endosperm, while SSI synthesizes the short chain in the vegetative organ as the same in the endosperm.
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- 2022
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8. Adenocarcinoma of the stomach and esophagogastric junction with low DNA methylation show poor prognoses
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Masayuki Urabe, Keisuke Matsusaka, Tetsuo Ushiku, Masaki Fukuyo, Bahityar Rahmutulla, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama, and Atsushi Kaneda
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Cancer Research ,Oncology ,Gastroenterology ,General Medicine - Abstract
Gastric cancer (GC) is characterized by unique DNA methylation epigenotypes (MEs). However, MEs including adenocarcinomas of the esophagogastric junction (AEG) and background non-neoplastic columnar mucosae (NM) remain to be clarified.We analyzed the genome-wide DNA MEs of AEG, GC, and background NM using the Infinium 450 k beadarray, followed by quantitative pyrosequencing validation. Large-scale data from The Cancer Genome Atlas (TCGA) were also reviewed.Unsupervised two-way hierarchical clustering using Infinium data of 21 AEG, 30 GC, and 11 NM revealed four DNA MEs: extremely high-ME (E-HME), high-ME (HME), low-ME (LME), and extremely low-ME (E-LME). Promoter methylation levels were validated by pyrosequencing in 146 samples. Non-inflammatory normal mucosae were clustered into E-LME, whereas gastric or esophagogastric junction mucosae with chronic inflammatory changes caused by either Helicobacter pylori infection or reflux esophagitis were clustered together into LME, suggesting that inflammation status determined DNA MEs regardless of the cause. Three cases of Barrett's-related adenocarcinoma were clustered into HME. Among 94 patients whose tumors could be clustered into one of four MEs, 11 patients with E-LME cancers showed significantly shorter overall survival than that in the other MEs, even with the multivariate Cox regression estimate. TCGA data also showed enrichment of AEG in HME and a poorer prognosis in E-LME.E-LME cases, newly confirmed in this study, form a unique subtype with poor prognosis that is not associated with inflammation-associated elevation of DNA methylation levels. LME could be acquired via chronic inflammation, regardless of the cause, and AEG might preferentially show HME.
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- 2022
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9. Human Digital Twins for Well-being
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Atsushi Fukayama, Shin-ichiro Eitoku, Iwaki Toshima, and Shiro Ozawa
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- 2022
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10. Whether Contribution of Features Differ Between Video-Mediated and In-Person Meetings in Important Utterance Estimation
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Fumio Nihei, Ryo Ishii, Yukiko I. Nakano, Atsushi Fukayama, and Takao Nakamura
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- 2023
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11. Development and multi‐institutional validation of an artificial intelligence‐based diagnostic system for gastric biopsy
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Hiroyuki, Abe, Yusuke, Kurose, Shusuke, Takahama, Ayako, Kume, Shu, Nishida, Miyako, Fukasawa, Yoichi, Yasunaga, Tetsuo, Ushiku, Youichiro, Ninomiya, Akihiko, Yoshizawa, Kohei, Murao, Shin'ichi, Sato, Masaru, Kitsuregawa, Tatsuya, Harada, Masanobu, Kitagawa, and Masashi, Fukayama
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Cancer Research ,Oncology ,Artificial Intelligence ,Biopsy ,Stomach ,Humans ,General Medicine - Abstract
To overcome the increasing burden on pathologists in diagnosing gastric biopsies, we developed an artificial intelligence-based system for the pathological diagnosis of gastric biopsies (AI-G), which is expected to work well in daily clinical practice in multiple institutes. The multistage semantic segmentation for pathology (MSP) method utilizes the distribution of feature values extracted from patches of whole-slide images (WSI) like pathologists' "low-power view" information of microscopy. The training dataset included WSIs of 4511 gastric biopsy tissues from 984 patients. In tissue-level validation, MSP AI-G showed better accuracy (91.0%) than that of conventional patch-based AI-G (PB AI-G) (89.8%). Importantly, MSP AI-G unanimously achieved higher accuracy rates (0.946 ± 0.023) than PB AI-G (0.861 ± 0.078) in tissue-level analysis, when applied to the cohorts of 10 different institutes (3450 samples of 1772 patients in all institutes, 198-555 samples of 143-206 patients in each institute). MSP AI-G had high diagnostic accuracy and robustness in multi-institutions. When pathologists selectively review specimens in which pathologist's diagnosis and AI prediction are discordant, the requirement of a secondary review process is significantly less compared with reviewing all specimens by another pathologist.
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- 2022
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12. Septic Arthritis Caused by Haemophilus parainfluenzae: A Pediatric Case Report and Literature Review
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Haruka Fukayama, Shota Myojin, Takanori Funaki, Yoshitsugu Fukuda, Tomoo Nakamura, Akira Ishiguro, and Chikara Ogimi
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Microbiology (medical) ,Infectious Diseases ,Pediatrics, Perinatology and Child Health - Published
- 2023
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13. The relationship between β-amylase and the degradation of starch temporarily stored in rice leaf blades
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Yu Sugimura, Hiroshi Fukayama, Hiroyasu Michiyama, and Tatsuya Hirano
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Organic Chemistry ,General Medicine ,Molecular Biology ,Applied Microbiology and Biotechnology ,Biochemistry ,Analytical Chemistry ,Biotechnology - Abstract
Starch is stored temporarily in the leaves during the day but degraded during the night. In this study, we investigated the relationship between diurnal changes in starch content in rice leaf blades and the mRNA levels of β-amylase genes. In addition to the known plastid-type β-amylases OsBAM2 and OsBAM3, OsBAM4, and OsBAM5 were also identified as plastid targeted proteins. In the leaf blades, starch contents, which reached its maximum at the end of day, showed two periods of marked decrease: from 18:00 to 21:00 and from 24:00 to 6:00. The expression of OsBAM2, OsBAM3, OsBAM4, and OsBAM5 was maintained at a low level from 18:00 to 21:00 but increased strongly after midnight. Furthermore, β-amylase activity gradually increased after 21:00, reaching a maximum during the early morning. These results suggest that in rice leaf blades, β-amylase plays an important role in starch degradation by being highly active from midnight to dawn.
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- 2023
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14. Lost expression of AT‐rich interaction domain 1A in the gastric mucosa—A constituent of field cancerization in the stomach
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Hiroyuki Abe, Hirofumi Rokutan, Yasushi Totoki, Hiromi Nakamura, Tatsuhiro Shibata, Tetsuo Ushiku, and Masashi Fukayama
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General Medicine ,Pathology and Forensic Medicine - Published
- 2023
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15. Data from Distinct Chemopreventive Effects of Aspirin in Diffuse and Intestinal-Type Gastric Cancer
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Kazuhiko Koike, Masashi Fukayama, Mitsuhiro Fujishiro, Tetsuo Ushiku, Atsuo Yamada, Sozaburo Ihara, Nobumi Suzuki, Mitsuru Konishi, Yoshihiro Hirata, Yoku Hayakawa, and Ryota Niikura
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Introduction: Although aspirin/NSAIDs may have potential preventive effects on several cancers, it remains unclear on gastric cancer. The purpose of this study is to compare the risk of developing gastric cancer and the histologic changes of intestinal metaplasia and neutrophil infiltration, between aspirin/NSAID users and nonusers.Methods: Using an electronic endoscopy database in two hospitals from 1996 to 2017, we analyzed the data from patients with chronic gastritis who received aspirin or NSAIDs prior to upper gastrointestinal endoscopy. One-to-one propensity score matching was performed to compare the proportion of gastric cancer, intestinal metaplasia, and neutrophil infiltration between these drug users and nonusers.Results: We analyzed 2,082 aspirin users and 2,082 nonusers as well as 898 NSAID users and 898 nonusers. Six diffuse-type and 19 intestinal-type gastric cancer, 1,243 intestinal metaplasia, and 1,503 neutrophil infiltration patients were identified. The proportion of diffuse-type gastric cancer (0.05%) was 80% lower in aspirin users compared with the nonusers (0.24%), and there was no case of diffuse-type cancer in patients who took aspirin for more than 2 years. In contrast, intestinal-type gastric cancer incidence was significantly higher in aspirin users (0.72%) compared with nonusers (0.14%). No significant differences in the incidence of gastric cancer were found between NSAID use and nonusers. NSAID use was significantly associated with decreased proportion of neutrophil infiltration compared with nonusers.Conclusion: Aspirin may have distinct effects between intestinal-type and diffuse-type gastric cancer development. Cancer Prev Res; 11(5); 279–86. ©2018 AACR.
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- 2023
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16. Supplementary Tables from Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite Instability–High Colorectal Cancers
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Hiroyuki Mano, Toshiaki Watanabe, Hiroyuki Aburatani, Masashi Fukayama, Hisae Iinuma, Yoshihiro Yamashita, Eirin Sai, Shinji Kohsaka, Takafumi Oga, Manabu Soda, Hiroyuki Abe, Genta Nagae, Shinya Kojima, Toshihide Ueno, Yoko Yamamoto, Masahito Kawazu, and Kazuhito Sato
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Supplementary Tables S1-S12: Supplementary Table S1: Primer sequences used in this study. Supplementary Table S2: Clinical information of tumours analysed in the present study. Supplementary Table S3: Patients' characteristics. Supplementary Table S4: Likely causal mutations in mismatch repair genes detected in this study. Supplementary Table S5: List of Tier 2 mutations. Supplementary Table S6: Significantly mutated genes identified with MutSigCV. Supplementary Table S7: Genes differentially altered between Lynch syndrome-associated/Lynch-like tumours and MLH1 promoter-methylated tumours. Supplementary Table S8: Recurrent copy number alterations detected with allele-specific copy number analysis. Supplementary Table S9: Pathways detected from top 209 Tier 2 genes with The Database for Annotation, Visualization and Integrated Discovery. Supplementary Table S10: Pathways detected from significantly mutated genes with The Database for Annotation, Visualization and Integrated Discovery. Supplementary Table S11: Detected oncogenic alterations and associated mutations with uncertain significance. Supplementary Table S12: Complementary DNA sequences of fusion points confirmed by reverse-transcription polymerase chain reaction followed by Sanger sequencing.
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- 2023
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17. Data from Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite Instability–High Colorectal Cancers
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Hiroyuki Mano, Toshiaki Watanabe, Hiroyuki Aburatani, Masashi Fukayama, Hisae Iinuma, Yoshihiro Yamashita, Eirin Sai, Shinji Kohsaka, Takafumi Oga, Manabu Soda, Hiroyuki Abe, Genta Nagae, Shinya Kojima, Toshihide Ueno, Yoko Yamamoto, Masahito Kawazu, and Kazuhito Sato
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Purpose:Colorectal cancers with microsatellite instability–high (MSI-H) status, due to mismatch repair deficiency, are associated with poor patient outcomes after relapse. We aimed to identify novel therapeutic targets for them.Experimental Design:We performed MSI analyses of over 2,800 surgically resected colorectal tumors obtained from consecutive patients treated in Japan from 1998 through June 2016. Whole-exome sequencing, transcriptome sequencing, and methylation analyses were performed on 149 of 162 tumors showing MSI in BAT25 and BAT26 loci. We analyzed patient survival times using Bonferroni-adjusted log-rank tests.Results:Sporadic MSI-H colorectal cancers with promoter methylation of MLH1 (called MM) had a clinicopathological profile that was distinct from that of colorectal cancers of patients with germline mutations (Lynch syndrome, LS-associated) or somatic, Lynch-like mutations in mismatch repair genes. MM tumors had more insertions and deletions and more recurrent mutations in BRAF and RNF43 than LS-associated or Lynch-like MSI-H tumors. Eleven fusion kinases were exclusively detected in MM MSI-H colorectal cancers lacking oncogenic KRAS/BRAF missense mutations and were associated with worse post-relapse prognosis. We developed a simple method to identify MM tumors and applied it to a validation cohort of 28 MSI-H colorectal cancers, identifying 16 MM tumors and 2 fusion kinases.Conclusions:We discovered that fusion kinases are frequently observed among sporadic MM MSI-H colorectal cancers. The new method to identify MM tumors enables us to straightforwardly group MSI-H patients into candidates of LS or fusion kinase carriers.
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- 2023
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18. Supplementary Figure Legends from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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PDF file - 107KB
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- 2023
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19. Supplementary Figure 4 from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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PDF file - 139KB, mRNA expression signal intensities in stem cells from the duodenum of Lgr5 Cre+ Catnblox(deltaex3) Klf5+/+ mice (x-axis, log) and Lgr5 Cre+ Catnblox(deltaex3) Klf5delta/delta mice (yaxis, log).
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- 2023
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20. Supplementary Figure 1 from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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PDF file - 674KB, Experimental design for the sorting of stem cells and TA cells from the duodenum of Lgr5-GFP-IRES-CreERT mice (Lgr5 Cre+ Catnb+/lox(ex3) Klf5flox/flox, Lgr5 Cre+ Catnb+/lox(ex3) Klf5+/+, and Lgr5 Cre+ Klf5flox/flox) for mRNA expression microarray analysis.
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- 2023
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21. Supplementary Table 1 from Activation of DNA Methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of PTEN Gene in Gastric Carcinoma
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Masashi Fukayama, Kenzo Takada, Takashi Sakatani, Takeo Nakaya, Teppei Morikawa, Shumpei Ishikawa, Aya Shinozaki, Tetsuo Ushiku, Noriko Murakami, Hiroshi Uozaki, and Rumi Hino
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Supplementary Table 1 from Activation of DNA Methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of PTEN Gene in Gastric Carcinoma
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- 2023
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22. Data from Classification of Epstein–Barr Virus–Positive Gastric Cancers by Definition of DNA Methylation Epigenotypes
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Masashi Fukayama, Hiroyuki Aburatani, Kenzo Takada, Yasuyuki Seto, Hiroshi Uozaki, Rumi Hino, Yasuko Kikuchi, Tetsuo Ushiku, Genta Nagae, Atsushi Kaneda, and Keisuke Matsusaka
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Epstein–Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has not been fully clarified. We analyzed promoter methylation in gastric cancer cases with Illumina's Infinium BeadArray and used hierarchical clustering analysis to classify gastric cancers into 3 subgroups: EBV−/low methylation, EBV−/high methylation, and EBV+/high methylation. The 3 epigenotypes were characterized by 3 groups of genes: genes methylated specifically in the EBV+ tumors (e.g., CXXC4, TIMP2, and PLXND1), genes methylated both in EBV+ and EBV−/high tumors (e.g., COL9A2, EYA1, and ZNF365), and genes methylated in all of the gastric cancers (e.g., AMPH, SORCS3, and AJAP1). Polycomb repressive complex (PRC) target genes in embryonic stem cells were significantly enriched among EBV−/high-methylation genes and commonly methylated gastric cancer genes (P = 2 × 10−15 and 2 × 10−34, respectively), but not among EBV+ tumor-specific methylation genes (P = 0.2), suggesting a different cause for EBV+-associated de novo methylation. When recombinant EBV was introduced into the EBV−/low-methylation epigenotype gastric cancer cell, MKN7, 3 independently established subclones displayed increases in DNA methylation. The promoters targeted by methylation were mostly shared among the 3 subclones, and the new methylation changes caused gene repression. In summary, DNA methylation profiling classified gastric cancer into 3 epigenotypes, and EBV+ gastric cancers showed distinct methylation patterns likely attributable to EBV infection. Cancer Res; 71(23); 7187–97. ©2011 AACR.
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- 2023
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23. Supplementary Methods, Tables 1-5, Figures 1-4 from Classification of Epstein–Barr Virus–Positive Gastric Cancers by Definition of DNA Methylation Epigenotypes
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Masashi Fukayama, Hiroyuki Aburatani, Kenzo Takada, Yasuyuki Seto, Hiroshi Uozaki, Rumi Hino, Yasuko Kikuchi, Tetsuo Ushiku, Genta Nagae, Atsushi Kaneda, and Keisuke Matsusaka
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- 2023
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24. Data from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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The intestinal epithelium maintains homeostasis by a self-renewal process involving resident stem cells, including Lgr5+ crypt-base columnar cells, but core mechanisms and their contributions to intestinal cancer are not fully defined. In this study, we examined a hypothesized role for KLF5, a zinc-finger transcription factor that is critical to maintain the integrity of embryonic and induced pluripotent stem cells, in intestinal stem-cell integrity and cancer in the mouse. Klf5 was indispensable for the integrity and oncogenic transformation of intestinal stem cells. In mice, inducible deletion of Klf5 in Lgr5+ stem cells suppressed their proliferation and survival in a manner associated with nuclear localization of β-catenin (Catnb), generating abnormal apoptotic cells in intestinal crypts. Moreover, production of lethal adenomas and carcinomas by specific expression of an oncogenic mutant of β-catenin in Lgr5+ stem cells was suppressed completely by Klf5 deletion in the same cells. Given that activation of the Wnt/β-catenin pathway is the most frequently altered pathway in human colorectal cancer, our results argue that KLF5 acts as a fundamental core regulator of intestinal oncogenesis at the stem-cell level, and they suggest KLF5 targeting as a rational strategy to eradicate stem-like cells in colorectal cancer. Cancer Res; 74(10); 2882–91. ©2014 AACR.
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- 2023
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25. Supplementary Tables 1 - 18 from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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XLS file - 1363KB, Supplementary Table 1. Genes downregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klfflox/flox mice, compared with Lgr5-EGFPires-CreERT2 atnblox(deltaex3) Klf5+/+ mice, under simultaneous induction of an active mutant of Catnb. Supplementary Table 2. Genes upregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFPires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous inductions of an active mutant of Catnb. Supplementary Table 3. Genes downregulated following the inducible deletion of Klf5 in the duodenal TA cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFPires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous induction of an active 6 mutant of Catnb. Supplementary Table 4. Genes upregulated following the inducible deletion of Klf5 in the duodenal TA cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFPires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous induction of an active mutant of Catnb. Supplementary Table 5. Genes downregulated following the inducible deletion of Klf5 in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous induction of an active mutant of Catnb. Supplementary Table 6. Genes upregulated following the inducible deletion of Klf5 in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous induction of an 7 active mutant of Catnb. Genes with fold change in expression (Lgr5 Cre+ Catnblox(deltaex3) Klf5delta/delta / Lgr5 Cre+ Catnblox(deltaex3) Klf5+/+) > 2 are listed in alphabetical order of official gene symbol. Supplementary Table 7. Genes downregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice. Supplementary Table 8. Genes upregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice. Supplementary Table 9. Genes downregulated following the inducible deletion of Klf5 in the duodenal TA cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice. Supplementary Table 10. Genes upregulated following the inducible deletion of Klf5 in the duodenal TA cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice. Supplementary Table 11. Genes downregulated following the inducible deletion of Klf5 in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFPires-CreERT2 Klf5flox/flox mice. Supplementary Table 12. Genes upregulated following the inducible deletion of Klf5 in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFPires-CreERT2 Klf5flox/flox mice. Supplementary Table 13. Genes downregulated following the inducible deletion of Klf5 in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under the simultaneous inductions 9 of an active mutant of Catnb, as well as downregulated in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice, without induction of the active mutant of Catnb. In other words, the genes with all fold changes < 0.5 are listed. Supplementary Table 14. Genes upregulated following the inducible deletion of Klf5 in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under the simultaneous inductions of an active mutant of Catnb, as well as downregulated in both duodenal stem cells and TA cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice, without induction of the active mutant of Catnb. In other words, the genes with all fold changes > 2 are listed. Supplementary Table 15. MicroRNAs downregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous induction of an active mutant of Catnb. MicroRNAs with fold change in expression (Lgr5 Cre+ Catnblox(deltaex3) Klf5delta/delta / Lgr5 Cre+ Catnblox(deltaex3) Klf5+/+) < 0.5 are listed in order of ascending fold change. Supplementary Table 16. Supplementary Table S16. MicroRNAs upregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5flox/flox mice, compared with Lgr5-EGFP-ires-CreERT2 Catnblox(deltaex3) Klf5+/+ mice, under simultaneous inductions of an active mutant of Catnb. Supplementary Table 17. MicroRNAs downregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice. Supplementary Table 18. MicroRNAs upregulated following the inducible deletion of Klf5 in the duodenal stem cells of Lgr5-EGFP-ires-CreERT2 Klf5delta/delta mice, compared with Lgr5-EGFP-ires-CreERT2 Klf5flox/flox mice.
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26. Data from Activation of DNA Methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of PTEN Gene in Gastric Carcinoma
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Masashi Fukayama, Kenzo Takada, Takashi Sakatani, Takeo Nakaya, Teppei Morikawa, Shumpei Ishikawa, Aya Shinozaki, Tetsuo Ushiku, Noriko Murakami, Hiroshi Uozaki, and Rumi Hino
- Abstract
CpG island promoter methylation of tumor suppressor genes is one of the most characteristic abnormalities in EBV-associated gastric carcinoma (GC). Aberrant promoter methylation and expression loss of PTEN were evaluated in cancer tissues of GC by methylation-specific PCR and immunohistochemistry, respectively, showing that both abnormalities occurred concurrently in EBV-associated GC. PTEN abnormalities were reiterated in GC cell lines MKN-1 and MKN-7 infected with recombinant EBV, and DNA methyltransferase 1 (DNMT1) was commonly overexpressed in both cell lines. Stable and transient transfection systems in MKN-1 similarly showed that viral latent membrane protein 2A (LMP2A) up-regulated DNMT1, leading to an increase in methylation of the PTEN promoter. Importantly, the level of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased in the nuclei of LMP2A-expressing GC cells, and knockdown of STAT3 counteracted LMP2A-mediated DNMT1 overexpression. Immunohistochemistry for both pSTAT3 and DNMT1 showed diffuse labeling in the nuclei of the cancer cells in GC tissues, especially in EBV-associated GC. Taken together, LMP2A induces the phosphorylation of STAT3, which activates DNMT1 transcription and causes PTEN expression loss through CpG island methylation of the PTEN promoter in EBV-associated GC. LMP2A plays an essential role in the epigenetic abnormalities in host stomach cells and in the development and maintenance of EBV-associated cancer. [Cancer Res 2009;69(7):2766–74]
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27. Supplementary Figure 2 from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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PDF file - 123KB, mRNA expression signal intensities in stem cells of the duodenum of Lgr5 Cre+ Klf5flox/flox mice without Klf5 deletion (x-axis, log) and Lgr5 Cre+ Klf5delta/delta mice (with Klf5 2 deletion) (y-axis, log).
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28. Supplementary Figure 3 from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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PDF file - 36KB, Mating strategy for generating Lgr5 Cre+ Catnb+/lox(ex3) Klf5flox/flox mice. Lgr5 Cre+ (Lgr5-EGFP-ires-CreERT2) mice had the activation of Cre recombinase, specific in Lgr5+ intestinal epithelial stem cells, by the intraperitoneal medication of Tamoxifen.
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29. Supplementary Materials and Methods from KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
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Ryozo Nagai, Masahiko Kuroda, Masashi Fukayama, Hans Clevers, Kazuki Nakao, Makoto M. Taketo, Toshiro Sato, Masashi Sanada, Masami Tanaka, Ichiro Manabe, Seishi Ogawa, and Takeo Nakaya
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PDF file - 116KB
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30. Interleukin-17 pathway inhibition with brodalumab in early systemic sclerosis: Analysis of a single-arm, open-label, phase 1 trial
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Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Ebata, Maiko Fukayama, Ai Kuzumi, Yuta Norimatsu, Kazuki M. Matsuda, Hirohito Kotani, Hayakazu Sumida, Asako Yoshizaki-Ogawa, Hisashi Kagebayashi, and Shinichi Sato
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Dermatology - Published
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31. Relations of Working Caregiver Work–family Conflicts to Assessment of Care Manager Support for Continued Employment and to Working Caregiver Characteristics
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Kaori Fukayama and Ayumi Kono
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General Medicine - Published
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32. Singer Diarization for Polyphonic Music With Unison Singing
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Hitoshi Suda, Daisuke Saito, Satoru Fukayama, Tomoyasu Nakano, and Masataka Goto
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Computational Mathematics ,Acoustics and Ultrasonics ,Computer Science (miscellaneous) ,Electrical and Electronic Engineering - Published
- 2022
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33. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter J, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Puiggròs, Montserrat, Pulido-Tamayo, Sergio, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Raphael, Benjamin J, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reimand, Jüri, Reis-Filho, Jorge, Reuter, Victor, Reyes-Salazar, Iker, Reyna, Matthew A, Reynolds, Sheila M, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R, Roberts, Nicola D, Roberts, Steven A, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, 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Sereni, Elisabetta, Serra, Stefano, Shackleton, Mark, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Sidiropoulos, Nikos, Sieuwerts, Anieta M, Sieverling, Lina, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Waddell, Nicola, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wala, Jeremiah A, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weischenfeldt, Joachim, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Mark H, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
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34. Additional file 1 of A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice
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Setogawa, Susumu, Kanda, Ryota, Tada, Shuto, Hikima, Takuya, Saitoh, Yoshito, Ishikawa, Mikiko, Nakada, Satoshi, Seki, Fumiko, Hikishima, Keigo, Matsumoto, Hideyuki, Mizuseki, Kenji, Fukayama, Osamu, Osanai, Makoto, Sekiguchi, Hiroto, and Ohkawa, Noriaki
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Supplementary Material 1
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- 2023
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35. Domain Adaptive Multiple Instance Learning for Instance-level Prediction of Pathological Images
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Takahama, Shusuke, Kurose, Yusuke, Mukuta, Yusuke, Abe, Hiroyuki, Yoshizawa, Akihiko, Ushiku, Tetsuo, Fukayama, Masashi, Kitagawa, Masanobu, Kitsuregawa, Masaru, and Harada, Tatsuya
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FOS: Computer and information sciences ,Computer Vision and Pattern Recognition (cs.CV) ,Computer Science - Computer Vision and Pattern Recognition - Abstract
Pathological image analysis is an important process for detecting abnormalities such as cancer from cell images. However, since the image size is generally very large, the cost of providing detailed annotations is high, which makes it difficult to apply machine learning techniques. One way to improve the performance of identifying abnormalities while keeping the annotation cost low is to use only labels for each slide, or to use information from another dataset that has already been labeled. However, such weak supervisory information often does not provide sufficient performance. In this paper, we proposed a new task setting to improve the classification performance of the target dataset without increasing annotation costs. And to solve this problem, we propose a pipeline that uses multiple instance learning (MIL) and domain adaptation (DA) methods. Furthermore, in order to combine the supervisory information of both methods effectively, we propose a method to create pseudo-labels with high confidence. We conducted experiments on the pathological image dataset we created for this study and showed that the proposed method significantly improves the classification performance compared to existing methods., Comment: Accepted to ISBI 2023 (Oral). ISBI paper version
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- 2023
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36. Combined burden and functional impact tests for cancer driver discovery using DriverPower
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Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, 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Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Dhalla, Noreen, Dhani, Neesha C, Dhir, Rajiv, DiBiase, Anthony, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Faltas, Bishoy M, Fan, Daiming, Fan, Yu, Faquin, William C, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Field, Matthew A, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gao, Jianjiong, Gao, Shengjie, Garraway, Levi, Garred, Øystein, Garrison, Erik, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstung, Moritz, 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Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Jiao, Wei, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kaiser, Vera B, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Kato, Mamoru, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jihoon, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Yogesh, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Larsimont, Denis, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lazar, Alexander J, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Constance H, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Siliang, Li, Xiaobo, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lynch, Andy G, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Macintyre, Geoff, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, Matthew, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyano, Satoru, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Navarro, Fabio CP, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ossowski, Stephan, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Peter J, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V, Pedamallu, Chandra Sekhar, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Puiggròs, Montserrat, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reis-Filho, Jorge, Reuter, Victor, Reynolds, Sheila M, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R, Roberts, Nicola D, Roberts, Steven A, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Saini, Natalie, Saito-Adachi, Mihoko, Salcedo, Adriana, Salgado, Roberto, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shelton, Troy, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shringarpure, Suyash S, Shriver, Craig, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, 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Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Junjun, Zhang, Xiuqing, Zhang, Zemin, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
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- 2023
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37. Deepwater response in the African cultivated rice Oryza glaberrima
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Quanshu Luo, Daisuke Sasayama, Misaki Nakazawa, Tomoko Hatanaka, Hiroshi Fukayama, and Tetsushi Azuma
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Oryza barthii ,SNORKEL1/2 ,Oryza glaberrima ,deepwater response ,Agronomy and Crop Science ,African rice - Abstract
Partial submergence of Oryza sativa deepwater rice elicits enhancement of internodal elongation, referred to as deepwater response, conferred by three types of genes, SNORKEL1/2 (SK1/2), SEMIDWARF1 (SD1), and ACCELERATOR OF INTERNODE ELONGATION 1 (ACE1). We investigated the presence and expression of these genes in the African cultivated rice Oryza glaberrima and the relationship between these genes and the deepwater response of O. glaberrima. In 49 of the 50 accessions tested, one or two SK genes were identified, which could be divided into three types of SK1 and four types of SK2. The accessions with the SK2 type whose expression was induced by submergence demonstrated rapid internodal elongation under submergence. In most of these accessions, submergence also increased the expression of SD1 and ACE1 genes. However, the accessions did not possess the haplotype of SD1 that is associated with high deepwater response in O. sativa. In contrast, they possessed the type of ACE1 gene similar to that in O. sativa deepwater rice. These results indicate that the molecular mechanisms underlying induction of deepwater response in O. glaberrima are similar to that found in deepwater rice of O. sativa and suggest that most O. glaberrima cultivars, including upland cultivars, can exhibit rapid internodal elongation under submergence.
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- 2023
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- View/download PDF
38. Integrative pathway enrichment analysis of multivariate omics data
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Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, Claes, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M, Weischenfeldt, Joachim, Wheeler, David A, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian, Reimand, Jüri, Aaltonen, Lauri A, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, 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Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
- Published
- 2023
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39. Pathway and network analysis of more than 2500 whole cancer genomes
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
- Published
- 2023
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40. Divergent mutational processes distinguish hypoxic and normoxic tumours
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Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, 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Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, Matthew, Meyerson, William, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyano, Satoru, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakagawa, Hidewaki, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Navarro, Fabio CP, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nielsen, Morten Muhlig, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ossowski, Stephan, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter J, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Puiggròs, Montserrat, Pulido-Tamayo, Sergio, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Raphael, Benjamin J, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reimand, Jüri, Reis-Filho, Jorge, Reuter, Victor, Reyes-Salazar, Iker, Reyna, Matthew A, Reynolds, Sheila M, Rheinbay, Esther, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R, Roberts, Nicola D, Roberts, Steven A, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rubin, Mark A, Rubio-Perez, Carlota, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Sahinalp, S Cenk, Saini, Natalie, Saito-Adachi, Mihoko, Saksena, Gordon, Salcedo, Adriana, Salgado, Roberto, Salichos, Leonidas, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sander, Chris, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schumacher, Steven E, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shackleton, Mark, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Sidiropoulos, Nikos, Siebert, Reiner, Sieuwerts, Anieta M, Sieverling, Lina, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Waddell, Nicola, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wala, Jeremiah A, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weischenfeldt, Joachim, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, 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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
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- 2023
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41. Effects of knockout of CO2-responsive CCT protein, a regulator of starch synthesis on physiological characteristics of rice
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Miyagawa, Fumihiro, Shibatani, Naoki, Morita, Ryutaro, Sasayama, Daisuke, Hatanaka, Tomoko, Azuma, Tetsushi, and Fukayama, Hiroshi
- Abstract
CO2-Responsive CCT Protein (CRCT) is suggested to be a positive regulator of starch synthesis-related genes in the vegetative organs of rice. To investigate the physiological function of CRCT, we produced CRCT knockout lines by CRISPR/Cas9 system. CRCT knockout tended to slightly reduce photosynthetic performance and had some adverse effects on growth parameters such as tiller number and straw dry weight. The starch content in the leaf sheath of CRCT knockout lines was significantly lower than that of wild-type. qRT-PCR and RNA-seq analysis showed that sucrose treatment induced the expression of CRCT, which, in turn, induced many starch synthesis-related genes in wild-type, whereas this induction did not occur in CRCT knockout lines. In conclusion, our results suggest that sugar induction of starch synthesis-related genes is almost fully dependent on CRCT, making it a necessary factor for normal photosynthesis and growth of rice.
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- 2023
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- View/download PDF
42. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Sieverling, Lina, Hong, Chen, Koser, Sandra D, Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M, Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J, Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C, Alvarez, Eva G, Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C, Bowtell, David DL, Brors, Benedikt, Burns, Kathleen H, Campbell, Peter J, Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J, Edwards, Paul A, Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W, Gerstein, Mark, Gordenin, Dmitry A, Haan, David, Haber, James E, Hess, Julian M, Imielinski, Marcin, Jones, David TW, Ju, Young Seok, Kazanov, Marat D, Klimczak, Leszek J, Koh, Youngil, Korbel, Jan O, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G, Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio CP, Ossowski, Stephan, Pearson, John V, Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D, Roberts, Steven A, Rodriguez-Martin, Bernardo, Schumacher, Steven E, Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Stewart, Chip, Torrents, David, MC Tubio, Jose, Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A, Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chang, David K, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooke, Susanna L, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, 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Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Maruvka, Yosef E, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, William, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, 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Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
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- 2023
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43. Effect of repetitive motion intervention on self-avatar on the sense of self-individuality
- Author
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Tetsunari Inamura, Shinichirou Eitoku, Iwaki Toshima, Shinya Shimizu, Atsushi Fukayama, Shiro Ozawa, and Takao Nakamura
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- 2022
- Full Text
- View/download PDF
44. A design of forceps-type coincidence radiation detector for intraoperative LN diagnosis: clinical impact estimated from LNs data of 20 esophageal cancer patients
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Sodai Takyu, Miwako Takahashi, Susumu Aikou, Taiga Yamaya, Yasuyuki Seto, Yasuhiro Okumura, Koichi Yagi, Shuntaro Yoshimura, Toshimitsu Momose, and Masashi Fukayama
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Esophageal Neoplasms ,business.industry ,Detector ,Forceps ,General Medicine ,Esophageal cancer ,Surgical Instruments ,medicine.disease ,Particle detector ,Coincidence ,Dissection ,medicine.anatomical_structure ,Fluorodeoxyglucose F18 ,Lymphatic Metastasis ,Positron Emission Tomography Computed Tomography ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lymph Nodes ,Tomography ,business ,Nuclear medicine ,Lymph node ,Neoplasm Staging - Abstract
Purpose To reduce postoperative complications, intraoperative lymph node (LN) diagnosis with 18F-fluoro-2-deoxy-D-glucose (FDG) is expected to optimize the extent of LN dissection, leading to less invasive surgery. However, such a diagnostic device has not yet been realized. We proposed the concept of coincidence detection wherein a pair of scintillation crystals formed the head of the forceps. To estimate the clinical impact of this detector, we determined the cut-off value using FDG as a marker for intraoperative LN diagnosis in patients with esophageal cancer, the specifications needed for the detector, and its feasibility using numerical simulation. Methods We investigated the dataset including pathological diagnosis and radioactivity of 1073 LNs resected from 20 patients who underwent FDG-positron emission tomography followed by surgery for esophageal cancer on the same day. The specifications for the detector were determined assuming that it should measure 100 counts (less than 10% statistical error) or more within the intraoperative measurement time of 30 s. The detector sensitivity was estimated using GEANT4 simulation and the expected diagnostic ability was calculated. Results The cut-off value was 620 Bq for intraoperative LN diagnosis. The simulation study showed that the detector had a radiation detection sensitivity of 0.96%, which was better than the estimated specification needed for the detector. Among the 1035 non-metastatic LNs, 815 were below the cut-off value. Conclusion The forceps-type coincidence detector can provide sufficient sensitivity for intraoperative LN diagnosis. Approximately 80% of the prophylactic LN dissections in esophageal cancer can be avoided using this detector.
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- 2021
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45. Rattractor - Instant guidance of a rat into a virtual cage using a deep brain stimulation
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Naoki Sudo, Sei-etsu Fujiwara, Takashi Isoyama, and Osamu Fukayama
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We developed “Rattractor” (rat attractor), a system to apply electrical stimuli to the deep brain of a rat as it stays in a specified region or a virtual cage to demonstrate an instant electrophysiological feedback controller for animals.Two wire electrodes were implanted in the brains of nine rats. The electrodes targeted the medial forebrain bundle (MFB), which is a part of the reward system in the deep brain. Following the recovery period, the rats were placed in a plain field where they could move freely, but wired to a stimulation circuit. An image sensor installed over the field detected the subject’s position, which triggered the stimulator such that the rat remained within the virtual cage. We conducted a behavioral experiment to evaluate the sojourn ratio of rats residing in the region. Thereafter, a histological analysis of the rat brain was performed to confirm the position of the stimulation sites in the brain.Seven rats survived the surgery and the recovery period without technical failures such as connector breaks. We observed that three of them tended to stay in the virtual cage during stimulation, and this effect was maintained for two weeks. Histological analysis revealed that the electrode tips were correctly placed in the MFB region of the rats. The other four subjects showed no apparent preference for the virtual cage. In these rats, we did not find electrode tips in the MFB, or could not determine their positions.Almost half of the rats tended to remain inside the virtual cage when position-related reward stimuli were triggered in the MFB region. Notably, our system did not require previous training or sequential interventions to affect the behavioral preferences of subjects. This process is similar to the situation in which sheep are chased by a shepherd dog in the desired direction.
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- 2022
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46. A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice
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Susumu Setogawa, Ryota Kanda, Shuto Tada, Takuya Hikima, Yoshito Saitoh, Mikiko Ishikawa, Satoshi Nakada, Fumiko Seki, Keigo Hikishima, Hideyuki Matsumoto, Kenji Mizuseki, Osamu Fukayama, Makoto Osanai, Hiroto Sekiguchi, and Noriaki Ohkawa
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Cellular and Molecular Neuroscience ,Molecular Biology - Abstract
Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.
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- 2022
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47. Exploiting Fine-tuning of Self-supervised Learning Models for Improving Bi-modal Sentiment Analysis and Emotion Recognition
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Wei Yang, Satoru Fukayama, Panikos Heracleous, and Jun Ogata
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- 2022
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48. Determining most suitable listener backchannel type for speaker's utterance
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Akira Morikawa, Ryo Ishii, Hajime Noto, Atsushi Fukayama, and Takao Nakamura
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- 2022
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49. Human Leukocyte Antigen Class I Deficiency in Gastric Carcinoma
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Akiko Iwasaki, Sho Yamazawa, Akiko Kunita, Yasuyuki Seto, Tetsuo Ushiku, Masashi Fukayama, Hiroharu Yamashita, Yasuyoshi Sato, and Aya Shinozaki-Ushiku
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Adult ,Male ,Epstein-Barr Virus Infections ,Human leukocyte antigen ,B7-H1 Antigen ,Virus ,Pathology and Forensic Medicine ,Lymphocytes, Tumor-Infiltrating ,Immune system ,Stomach Neoplasms ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,Histocompatibility Antigens Class I ,Cancer ,Middle Aged ,medicine.disease ,digestive system diseases ,Immune checkpoint ,Blockade ,Cancer research ,Biomarker (medicine) ,Female ,Microsatellite Instability ,Tumor Escape ,Surgery ,Anatomy ,business ,Infiltration (medical) - Abstract
Immune checkpoint inhibitor therapy is effective only for a subset of patients with gastric cancer. Impaired neoantigen presentation caused by deficiency of human leukocyte antigen class I (HLA-I) has been reported as a common mechanism of immune evasion which is associated with resistance to immune checkpoint blockade. To elucidate the significance of HLA-I deficiency in gastric cancer with special focus on microsatellite instable (MSI) and Epstein-Barr virus (EBV)-positive tumors, we examined HLA-I expression on tumor cells and correlated the results with clinicopathologic features, programmed death-ligand 1 (PD-L1) expression, and degree of tumor-infiltrating immune cells. This study included 58 MSI, 44 EBV-positive, and 107 non-EBV non-MSI tumors for comparison. The frequency of HLA-I deficiency (≥1% tumor cells) was significantly higher in MSI tumors (52%) compared with EBV-positive tumors (23%) and the other tumors (28%). In contrast, PD-L1 expression levels were highest in EBV-positive tumors, followed by MSI tumors, with the lowest prevalence in the other tumors in both Tumor Proportion Score and Combined Positive Score. HLA-I deficiency was significantly more frequent in advanced tumors (pT2-4) than in early tumors (pT1) in MSI and non-EBV non-MSI subtypes. In addition, the degree of CD8-positive cells infiltration was significantly reduced in HLA-I deficient tumor areas compared with HLA-I preserved tumor area within a tumor. Based on our observations, HLA-I, as well as PD-L1, should be considered as a common mechanism of immune escape especially in the MSI subtype, and therefore could be a biomarker predicting response to immune checkpoint inhibitor therapy in gastric cancer.
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- 2021
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50. Growth responses of seedlings under complete submergence in rice cultivars carrying both the submergence-tolerance gene SUB1A-1 and the floating genes SNORKELs
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Quanshu Luo, Tetsushi Azuma, Hiroshi Fukayama, Daisuke Sasayama, Shunsuke Oe, and Tomoko Hatanaka
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floating rice ,Oryza sativa ,rice ,Plant culture ,food and beverages ,Deepwater rice ,flood ,Biology ,SB1-1110 ,Horticulture ,Cultivar ,submergence tolerance ,ethylene response factor ,Agronomy and Crop Science ,Gene - Abstract
We screened 80 Asian rice (Oryza sativa L.) cultivars for the presence of the submergence-tolerance gene SUB1A-1 and the floating genes SNORKEL1 (SK1) and SNORKEL2 (SK2), and found that the deepwater rice cultivar Baisbish (BSB) and the submergence-tolerant cultivar Flood Resistant 13A (FR13A) both possess the SUB1A-1 and the SK1/2. When BSB and FR13A seedlings were completely submerged, spindly growth of shoots was induced in BSB but not in FR13A. Submergence significantly increased the SUB1A-1 transcript abundance in BSB and FR13A shoots, but the expression level in BSB was much lower than that of FR13A. Submergence also induced the expression of both ERF66 and ERF67, the transcriptional targets of SUB1A-1, in FR13A shoots, whereas it upregulated the expression of ERF67 but not that of ERF66 in BSB shoots. These results suggest that BSB could not display submergence tolerance due to the low expression of SUB1A-1 and/or ERF66 under submergence.
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- 2021
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