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Abstract In cancer genome analysis, identifying pathogenic alterations and assessing their effects on oncogenic processes is important. Although whole exome sequencing (WES) can effectively detect such changes, driver alterations could not be identified in 27.8% of the cases, according to a previous study. The objectives of the present study were to evaluate the utility of whole genome sequencing (WGS) and clarify its differences with WES in terms of driver alteration detection. For this purpose, WGS analysis was conducted on 177 driverless WES samples, selected from 5,480 fresh frozen samples derived from 5,140 Japanese patients with cancer. These samples were selected as primary tumor, both WES and transcriptome profiling were performed, estimated tumor content of ≥ 30%, and no driver alterations were identified by WES. WGS identified driver and likely driver alterations in 68.4 and 22.6% of the samples, respectively. The most frequent alteration type was oncogene amplification, followed by tumor suppressor gene deletion and small variants located outside the coding region. In the remaining 9.0% of samples, no such signals were identified; therefore, further investigations are required. The current study clearly demonstrated the role and utility of WGS in identifying genomic alterations that contribute to tumorigenesis.

Abstract The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with sporadic tumor cells, low tumor content prevents the accurate detection of somatic alterations using targeted sequencing. To efficiently identify CNVs, we performed tumor cell enrichment using tissue suspensions of formalin-fixed paraffin-embedded (FFPE) tissue sections with low tumor cell content. Tumor-enriched and residual fractions were separated from FFPE tissue suspensions of intestinal and diffuse-type gastric cancers containing sporadic tumor cells, and targeted sequencing was performed on 225 cancer-related genes. Sequencing of a targeted panel of cancer-related genes using tumor-enriched fractions increased the number of detectable CNVs and the copy number of amplified genes. Furthermore, CNV analysis using the normal cell-enriched residual fraction as a reference for CNV scoring allowed targeted sequencing to detect CNV characteristics of diffuse-type gastric cancer with low tumor content. Our approach improves the CNV detection rate in targeted sequencing with tumor enrichment and the accuracy of CNV detection in archival samples without paired blood.

In the process of investigating synaptic changes happening to mutants lacking postsynaptic receptors in the neuromuscular junction, we focused on a hitherto uncharacterized zebrafish gene zgc153932 whose expression was increased in the RNAseq and droplet digital PCR (ddPCR) analysis of a paralyzed mutant sofa potato. The zgc153932 gene which we named omcin5 (omc5) showed amino acid sequence similarity to human uromodulin and GP2, which are expressed in epithelial cells of the kidney and the gut respectively and bind to bacteria pili. omc5 had 14 paralogues in a ∼400 KB region on the chromosome 12 of the zebrafish genome. These genes, named omcin1 through 15, constitute a gene cluster which presumably arose from recent gene duplications in the zebrafish lineage. An antibody raised against the epitope common to 6–9 genes in the omcin family revealed expression in the cloaca of 1 day post fertilization (dpf) embryos which broadened to the urinary and digestive tracts by 5 dpf. Expression of omc5 was increased by exposure of embryos to Escherichia coli (E. coli). Survival of omc5 mutant embryos was shortened in the presence of E. coli, or when they were not maintained in germ-free conditions. Adults omc5 mutants also exhibited susceptibility to infection. Other teleost species which had omcin-like genes in their genomes showed a range of gene duplication, resulting in clusters of 1 to >15 omcin-like genes. We hereby identified a new gene family specific to teleost that include a microbial induced gene which confers resistance to bacterial infection.

The relationship between the environment and marine animal small-scale behavior is not fully understood. This is largely due to the difficulty in obtaining environmental datasets with a high spatiotemporal precision. The problem is particularly pertinent in assessing the influence of environmental factors in rapid, high energy-consuming behavior such as seabird take-off. To fill the gaps in the existing environmental datasets, we employed novel techniques using animal-borne sensors with motion records to estimate wind and ocean wave parameters and evaluated their influence on wandering albatross take-off patterns. Measurements revealed that wind speed and wave heights experienced by wandering albatrosses during take-off ranged from 0.7 to 15.4 m/s and 1.6 to 6.4 m, respectively. The four indices measured (flapping number, frequency, sea surface running speed, and duration) also varied with the environmental conditions (e.g., flapping number varied from 0 to over 20). Importantly, take-off was easier under higher wave conditions than under lower wave conditions at a constant wind speed, and take-off effort increased only when both wind and waves were gentle. Our data suggest that both ocean waves and winds play important roles for albatross take-off and advances our current understanding of albatross flight mechanisms.

Abstract The differences in genetic susceptibility to lung adenocarcinoma and squamous cell carcinoma remain unclear. We developed a customized, targeted gene sequencing panel for efficient and sensitive identification of germline variants, including whole-gene deletion types for cancer-related drug-metabolizing enzyme genes in lung adenocarcinoma and squamous cell carcinoma. The minor allele frequencies of the variants, confirmed as clinically significant in the Japanese population, did not differ significantly from those of normal participants listed in the public database. Genotype analysis comparing lung adenocarcinoma (n = 559) and squamous cell carcinoma (n = 151) indicated that the variants of DPYD (rs190771411, Fisher’s exact test, P = 0.045; rs200562975, P = 0.045) and ALDH2 (rs568781254, P = 0.032) were associated with an increased risk of squamous cell carcinoma compared to adenocarcinoma. Conversely, whole-gene deletion of CYP2A6 was associated with adenocarcinoma but not squamous cell carcinoma. Notably, whole-gene deletion of CYP2A6 was confirmed in 22 patients with lung adenocarcinoma but not in any patients with squamous cell carcinoma. Most patients with whole-gene deletion of CYP2A6 were female non-smokers. The discovery of a whole-gene deletion of CYP2A6 in patients with lung adenocarcinoma may have an important role in clinical practice and advance our understanding of CYP2A6 germline variants and their association with carcinogenesis or their susceptibility to lung adenocarcinoma.

Abstract With the emergence of next-generation sequencing (NGS)-based cancer gene panel tests in routine oncological practice in Japan, an easily interpretable cancer genome database of Japanese patients in which mutational profiles are unaffected by racial differences is needed to improve the interpretation of the detected gene alterations. Considering this, we constructed the first Japanese cancer genome database, called the Japanese version of the Cancer Genome Atlas (JCGA), which includes multiple tumor types. The database includes whole-exome sequencing data from 4907 surgically resected primary tumor samples obtained from 4753 Japanese patients with cancer and graphically provides genome information on 460 cancer-associated genes, including the 336 genes that are included in two NGS-based cancer gene panel tests approved by the Pharmaceuticals and Medical Devices Agency. Moreover, most of the contents of this database are written in Japanese; this not only helps physicians explain the results of NGS-based cancer gene panel tests but also enables patients and their families to obtain further information regarding the detected gene alterations.

Abstract Background Mutation analysis using next-generation sequencing highlights the features of tumors with somatic alterations. However, the mutation profile of double cancer remains unclear. Here, we analyzed tumors derived from the same patient using whole exome sequencing (WES) to investigate the coherence of somatic mutations in double cancer. Methods First, the tumor mutational burden (TMB) was investigated using WES of 5521 tumor specimens from a Japanese pan-cancer cohort. The frequencies of mutation concordance were then compared in these cancers. Finally, we calculated the expected value of mutational concordance fitting a Poisson distribution to determine the relationship between double and metastatic cancers. Results In all, 44, 58, and 121 paired samples were diagnosed as double cancer, multifocal lesions (derived from identical tissues), and metastasis, respectively. Our analysis revealed that common somatic mutations were almost entirely absent in double cancer, whereas primary tumors and metastatic foci harbored several identical alterations. Concordance of the mutation profile in the same patient reflects the tumor origin and development, suggesting the potential for identifying double cancer based on common somatic mutations. Furthermore, according to a Poisson distribution, double cancer could be discriminated based on paired samples from the same patient. The probability of double cancer with more than 10 mutations was ≤1 part-per-billion (ppb, 10− 9). In multifocal lesions, 74% of tumor pairs accumulated ≤10 common mutations, implying a difference in tumor origin within identical tissues. Conclusions These findings indicate that counting common somatic mutations can indicate the differences in origin between tumors derived from the same patient. Our mutation coherence analysis can thus provide beneficial information for diagnosing double cancer.

The way goal-oriented birds adjust their travel direction and route in response to wind significantly affects their travel costs. This is expected to be particularly pronounced in pelagic seabirds, which utilize a wind-dependent flight style called dynamic soaring. Dynamic soaring seabirds in situations without a definite goal, e.g. searching for prey, are known to preferentially fly with crosswinds or quartering-tailwinds to increase the speed and search area, and reduce travel costs. However, little is known about their reaction to wind when heading to a definite goal, such as homing. Homing tracks of wandering albatrosses (Diomedea exulans) vary from beelines to zigzags, which are similar to those of sailboats. Here, given that both albatrosses and sailboats travel slower in headwinds and tailwinds, we tested whether the time-minimizing strategies used by yacht racers can be compared to the locomotion patterns of wandering albatrosses. We predicted that when the goal is located upwind or downwind, albatrosses should deviate their travel directions from the goal on the mesoscale and increase the number of turns on the macroscale. Both hypotheses were supported by track data from albatrosses and racing yachts in the Southern Ocean confirming that albatrosses qualitatively employ the same strategy as yacht racers. Nevertheless, albatrosses did not strictly minimize their travel time, likely making their flight robust against wind fluctuations to reduce flight costs. Our study provides empirical evidence of tacking in albatrosses and demonstrates that man-made movement strategies provide a new perspective on the laws underlying wildlife movement. [ABSTRACT FROM AUTHOR]

Animal telemetry is a powerful tool for observing marine animals and the physical environments that they inhabit, from coastal and continental shelf ecosystems to polar seas and open oceans. Satellite-linked biologgers and networks of acoustic receivers allow animals to be reliably monitored over scales of tens of meters to thousands of kilometers, giving insight into their habitat use, home range size, the phenology of migratory patterns and the biotic and abiotic factors that drive their distributions. Furthermore, physical environmental variables can be collected using animals as autonomous sampling platforms, increasing spatial and temporal coverage of global oceanographic observation systems. The use of animal telemetry, therefore, has the capacity to provide measures from a suite of essential ocean variables (EOVs) for improved monitoring of Earth's oceans. Here we outline the design features of animal telemetry systems, describe current applications and their benefits and challenges, and discuss future directions. We describe new analytical techniques that improve our ability to not only quantify animal movements but to also provide a powerful framework for comparative studies across taxa. We discuss the application of animal telemetry and its capacity to collect biotic and abiotic data, how the data collected can be incorporated into ocean observing systems, and the role these data can play in improved ocean management.