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2. A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

Author

Yao, Zizhen, van Velthoven, Cindy T. J., Kunst, Michael, Zhang, Meng, McMillen, Delissa, Lee, Changkyu, Jung, Won, Goldy, Jeff, Abdelhak, Aliya, Aitken, Matthew, Baker, Katherine, Baker, Pamela, Barkan, Eliza, Bertagnolli, Darren, Bhandiwad, Ashwin, Bielstein, Cameron, Bishwakarma, Prajal, Campos, Jazmin, Carey, Daniel, Casper, Tamara, Chakka, Anish Bhaswanth, Chakrabarty, Rushil, Chavan, Sakshi, Chen, Min, Clark, Michael, Close, Jennie, Crichton, Kirsten, Daniel, Scott, DiValentin, Peter, Dolbeare, Tim, Ellingwood, Lauren, Fiabane, Elysha, Fliss, Timothy, Gee, James, Gerstenberger, James, Glandon, Alexandra, Gloe, Jessica, Gould, Joshua, Gray, James, Guilford, Nathan, Guzman, Junitta, Hirschstein, Daniel, Ho, Windy, Hooper, Marcus, Huang, Mike, Hupp, Madie, Jin, Kelly, Kroll, Matthew, Lathia, Kanan, Leon, Arielle, Li, Su, Long, Brian, Madigan, Zach, Malloy, Jessica, Malone, Jocelin, Maltzer, Zoe, Martin, Naomi, McCue, Rachel, McGinty, Ryan, Mei, Nicholas, Melchor, Jose, Meyerdierks, Emma, Mollenkopf, Tyler, Moonsman, Skyler, Nguyen, Thuc Nghi, Otto, Sven, Pham, Trangthanh, Rimorin, Christine, Ruiz, Augustin, Sanchez, Raymond, Sawyer, Lane, Shapovalova, Nadiya, Shepard, Noah, Slaughterbeck, Cliff, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Valera Cuevas, Nasmil, Vance, Shane, Wadhwani, Katherine, Ward, Katelyn, Levi, Boaz, Farrell, Colin, Young, Rob, Staats, Brian, Wang, Ming-Qiang Michael, Thompson, Carol L., Mufti, Shoaib, Pagan, Chelsea M., Kruse, Lauren, Dee, Nick, Sunkin, Susan M., Esposito, Luke, Hawrylycz, Michael J., Waters, Jack, Ng, Lydia, Smith, Kimberly, Tasic, Bosiljka, Zhuang, Xiaowei, and Zeng, Hongkui

Published
2023
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3. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Author

Muus, Christoph, Luecken, Malte, Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik, Duong, Elizabeth, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam, Chung, Hattie, Montoro, Daniel, Adams, Taylor, Aliee, Hananeh, Allon, Samuel, Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh, Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas, Cuoco, Michael, Cuomo, Anna, Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David, Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin, Habermann, Arun, Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros, Kuo, Christin, Larsson, Ludvig, Leney-Greene, Michael, Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif, Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph, Mbano, Ian, McAdams, Alexi, Nabhan, Ahmad, Nyquist, Sarah, Penland, Lolita, Poirion, Olivier, Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas, Shea, Conor, Shi, Xingyi, Sinha, Rahul, Sit, Rene, Slowikowski, Kamil, Slyper, Michal, Smith, Neal, Sountoulidis, Alex, Strunz, Maximilian, and Sullivan, Travis

Subjects
Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, COVID-19, Cathepsin L, Datasets as Topic, Demography, Female, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Lung, Male, Middle Aged, Organ Specificity, Respiratory System, SARS-CoV-2, Sequence Analysis, RNA, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization
Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Published
2021

4. Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment

Author

Hwang, William L., Jagadeesh, Karthik A., Guo, Jimmy A., Hoffman, Hannah I., Yadollahpour, Payman, Reeves, Jason W., Mohan, Rahul, Drokhlyansky, Eugene, Van Wittenberghe, Nicholas, Ashenberg, Orr, Farhi, Samouil L., Schapiro, Denis, Divakar, Prajan, Miller, Eric, Zollinger, Daniel R., Eng, George, Schenkel, Jason M., Su, Jennifer, Shiau, Carina, Yu, Patrick, Freed-Pastor, William A., Abbondanza, Domenic, Mehta, Arnav, Gould, Joshua, Lambden, Conner, Porter, Caroline B. M., Tsankov, Alexander, Dionne, Danielle, Waldman, Julia, Cuoco, Michael S., Nguyen, Lan, Delorey, Toni, Phillips, Devan, Barth, Jaimie L., Kem, Marina, Rodrigues, Clifton, Ciprani, Debora, Roldan, Jorge, Zelga, Piotr, Jorgji, Vjola, Chen, Jonathan H., Ely, Zackery, Zhao, Daniel, Fuhrman, Kit, Fropf, Robin, Beechem, Joseph M., Loeffler, Jay S., Ryan, David P., Weekes, Colin D., Ferrone, Cristina R., Qadan, Motaz, Aryee, Martin J., Jain, Rakesh K., Neuberg, Donna S., Wo, Jennifer Y., Hong, Theodore S., Xavier, Ramnik, Aguirre, Andrew J., Rozenblatt-Rosen, Orit, Mino-Kenudson, Mari, Castillo, Carlos Fernandez-del, Liss, Andrew S., Ting, David T., Jacks, Tyler, and Regev, Aviv

Published
2022
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5. A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles

Author

Subramanian, Aravind, Narayan, Rajiv, Corsello, Steven M, Peck, David D, Natoli, Ted E, Lu, Xiaodong, Gould, Joshua, Davis, John F, Tubelli, Andrew A, Asiedu, Jacob K, Lahr, David L, Hirschman, Jodi E, Liu, Zihan, Donahue, Melanie, Julian, Bina, Khan, Mariya, Wadden, David, Smith, Ian C, Lam, Daniel, Liberzon, Arthur, Toder, Courtney, Bagul, Mukta, Orzechowski, Marek, Enache, Oana M, Piccioni, Federica, Johnson, Sarah A, Lyons, Nicholas J, Berger, Alice H, Shamji, Alykhan F, Brooks, Angela N, Vrcic, Anita, Flynn, Corey, Rosains, Jacqueline, Takeda, David Y, Hu, Roger, Davison, Desiree, Lamb, Justin, Ardlie, Kristin, Hogstrom, Larson, Greenside, Peyton, Gray, Nathanael S, Clemons, Paul A, Silver, Serena, Wu, Xiaoyun, Zhao, Wen-Ning, Read-Button, Willis, Wu, Xiaohua, Haggarty, Stephen J, Ronco, Lucienne V, Boehm, Jesse S, Schreiber, Stuart L, Doench, John G, Bittker, Joshua A, Root, David E, Wong, Bang, and Golub, Todd R

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Aetiology, 2.1 Biological and endogenous factors, Cell Line, Tumor, Drug Resistance, Neoplasm, Gene Expression Profiling, Humans, Neoplasms, Organ Specificity, Pharmaceutical Preparations, Sequence Analysis, RNA, Small Molecule Libraries, Functional genomics, chemical biology, gene expression profiling, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs, and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io.

Published
2017

6. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

Author

Delorey, Toni M., Ziegler, Carly G. K., Heimberg, Graham, Normand, Rachelly, Yang, Yiming, Segerstolpe, Åsa, Abbondanza, Domenic, Fleming, Stephen J., Subramanian, Ayshwarya, Montoro, Daniel T., Jagadeesh, Karthik A., Dey, Kushal K., Sen, Pritha, Slyper, Michal, Pita-Juárez, Yered H., Phillips, Devan, Biermann, Jana, Bloom-Ackermann, Zohar, Barkas, Nikolaos, Ganna, Andrea, Gomez, James, Melms, Johannes C., Katsyv, Igor, Normandin, Erica, Naderi, Pourya, Popov, Yury V., Raju, Siddharth S., Niezen, Sebastian, Tsai, Linus T.-Y., Siddle, Katherine J., Sud, Malika, Tran, Victoria M., Vellarikkal, Shamsudheen K., Wang, Yiping, Amir-Zilberstein, Liat, Atri, Deepak S., Beechem, Joseph, Brook, Olga R., Chen, Jonathan, Divakar, Prajan, Dorceus, Phylicia, Engreitz, Jesse M., Essene, Adam, Fitzgerald, Donna M., Fropf, Robin, Gazal, Steven, Gould, Joshua, Grzyb, John, Harvey, Tyler, Hecht, Jonathan, Hether, Tyler, Jané-Valbuena, Judit, Leney-Greene, Michael, Ma, Hui, McCabe, Cristin, McLoughlin, Daniel E., Miller, Eric M., Muus, Christoph, Niemi, Mari, Padera, Robert, Pan, Liuliu, Pant, Deepti, Pe’er, Carmel, Pfiffner-Borges, Jenna, Pinto, Christopher J., Plaisted, Jacob, Reeves, Jason, Ross, Marty, Rudy, Melissa, Rueckert, Erroll H., Siciliano, Michelle, Sturm, Alexander, Todres, Ellen, Waghray, Avinash, Warren, Sarah, Zhang, Shuting, Zollinger, Daniel R., Cosimi, Lisa, Gupta, Rajat M., Hacohen, Nir, Hibshoosh, Hanina, Hide, Winston, Price, Alkes L., Rajagopal, Jayaraj, Tata, Purushothama Rao, Riedel, Stefan, Szabo, Gyongyi, Tickle, Timothy L., Ellinor, Patrick T., Hung, Deborah, Sabeti, Pardis C., Novak, Richard, Rogers, Robert, Ingber, Donald E., Jiang, Z. Gordon, Juric, Dejan, Babadi, Mehrtash, Farhi, Samouil L., Izar, Benjamin, Stone, James R., Vlachos, Ioannis S., Solomon, Isaac H., Ashenberg, Orr, Porter, Caroline B. M., Li, Bo, Shalek, Alex K., Villani, Alexandra-Chloé, Rozenblatt-Rosen, Orit, and Regev, Aviv

Published
2021
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7. High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines

Author

Yu, Channing, Mannan, Aristotle M, Yvone, Griselda Metta, Ross, Kenneth N, Zhang, Yan-Ling, Marton, Melissa A, Taylor, Bradley R, Crenshaw, Andrew, Gould, Joshua Z, Tamayo, Pablo, Weir, Barbara A, Tsherniak, Aviad, Wong, Bang, Garraway, Levi A, Shamji, Alykhan F, Palmer, Michelle A, Foley, Michael A, Winckler, Wendy, Schreiber, Stuart L, Kung, Andrew L, and Golub, Todd R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Animals, Cell Line, Tumor, DNA Barcoding, Taxonomic, Drug Resistance, Neoplasm, Genotyping Techniques, High-Throughput Nucleotide Sequencing, Humans, Mice, Neoplasms
Abstract

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.

Published
2016

8. Highly multiplexed, image-based pooled screens in primary cells and tissues with PerturbView

Author

Kudo, Takamasa, primary, Meireles, Ana M, additional, Moncada, Reuben, additional, Chen, Yushu, additional, Wu, Ping, additional, Gould, Joshua, additional, Hu, Xiaoyu, additional, Kornfeld, Opher, additional, Jesudason, Rajiv, additional, Foo, Conrad, additional, Hockendorf, Burkhard, additional, Bravo, Hector Corrada, additional, Town, Jason P, additional, Wei, Runmin, additional, Rios, Antonio, additional, Chandrasekar, Vineethkrishna, additional, Heinlein, Melanie, additional, Cai, Shuangyi, additional, Lu, Cherry Sakura, additional, Celen, Cemre, additional, Kljavin, Noelyn, additional, Jiang, Jian, additional, Hleap, Jose Sergio, additional, Kayagaki, Nobuhiko, additional, Melo, Felipe de Sousa e, additional, McGinnis, Lisa, additional, Li, Bo, additional, Singh, Avtar, additional, Garraway, Levi, additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, and Lubeck, Eric, additional

Published
2023
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9. STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization

Author

Xu, Zhicheng, primary, Wang, Weiwen, additional, Yang, Tao, additional, Li, Ling, additional, Ma, Xizheng, additional, Chen, Jing, additional, Wang, Jieyu, additional, Huang, Yan, additional, Gould, Joshua, additional, Lu, Huifang, additional, Du, Wensi, additional, Sahu, Sunil Kumar, additional, Yang, Fan, additional, Li, Zhiyong, additional, Hu, Qingjiang, additional, Hua, Cong, additional, Hu, Shoujie, additional, Liu, Yiqun, additional, Cai, Jia, additional, You, Lijin, additional, Zhang, Yong, additional, Li, YuXiang, additional, Zeng, Wenjun, additional, Chen, Ao, additional, Wang, Bo, additional, Liu, Longqi, additional, Chen, Fengzhen, additional, Ma, Kailong, additional, Xu, Xun, additional, and Wei, Xiaofeng, additional

Published
2023
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11. A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors

Author

Slyper, Michal, Porter, Caroline B. M., Ashenberg, Orr, Waldman, Julia, Drokhlyansky, Eugene, Wakiro, Isaac, Smillie, Christopher, Smith-Rosario, Gabriela, Wu, Jingyi, Dionne, Danielle, Vigneau, Sébastien, Jané-Valbuena, Judit, Tickle, Timothy L., Napolitano, Sara, Su, Mei-Ju, Patel, Anand G., Karlstrom, Asa, Gritsch, Simon, Nomura, Masashi, Waghray, Avinash, Gohil, Satyen H., Tsankov, Alexander M., Jerby-Arnon, Livnat, Cohen, Ofir, Klughammer, Johanna, Rosen, Yanay, Gould, Joshua, Nguyen, Lan, Hofree, Matan, Tramontozzi, Peter J., Li, Bo, Wu, Catherine J., Izar, Benjamin, Haq, Rizwan, Hodi, F. Stephen, Yoon, Charles H., Hata, Aaron N., Baker, Suzanne J., Suvà, Mario L., Bueno, Raphael, Stover, Elizabeth H., Clay, Michael R., Dyer, Michael A., Collins, Natalie B., Matulonis, Ursula A., Wagle, Nikhil, Johnson, Bruce E., Rotem, Asaf, Rozenblatt-Rosen, Orit, and Regev, Aviv

Published
2020
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12. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy.

Author

Lohr, Jens, Stojanov, Petar, Carter, Scott, Cruz-Gordillo, Peter, Lawrence, Michael, Auclair, Daniel, Sougnez, Carrie, Knoechel, Birgit, Gould, Joshua, Saksena, Gordon, Cibulskis, Kristian, McKenna, Aaron, Chapman, Michael, Straussman, Ravid, Levy, Joan, Perkins, Louise, Keats, Jonathan, Schumacher, Steven, Rosenberg, Mara, Getz, Gad, and Golub, Todd

Subjects
Blotting, Western, Gene Dosage, Genetic Heterogeneity, Humans, Multiple Myeloma, Mutation, Sequence Analysis, DNA
Abstract

We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions.

Published
2014

13. High-definition spatial transcriptomics for in situ tissue profiling

Author

Vickovic, Sanja, Eraslan, Gökcen, Salmén, Fredrik, Klughammer, Johanna, Stenbeck, Linnea, Schapiro, Denis, Äijö, Tarmo, Bonneau, Richard, Bergenstråhle, Ludvig, Navarro, José Fernandéz, Gould, Joshua, Griffin, Gabriel K., Borg, Åke, Ronaghi, Mostafa, Frisén, Jonas, Lundeberg, Joakim, Regev, Aviv, and Ståhl, Patrik L.

Published
2019
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14. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Author

Straussman, Ravid, Morikawa, Teppei, Shee, Kevin, Barzily-Rokni, Michal, Qian, Zhi Rong, Du, Jinyan, Davis, Ashli, Mongare, Margaret M, Gould, Joshua, Frederick, Dennie T, Cooper, Zachary A, Chapman, Paul B, Solit, David B, Ribas, Antoni, Lo, Roger S, Flaherty, Keith T, Ogino, Shuji, Wargo, Jennifer A, and Golub, Todd R

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Cell Line, Tumor, Coculture Techniques, Drug Resistance, Neoplasm, Hepatocyte Growth Factor, Humans, Indoles, Melanoma, Molecular Targeted Therapy, Mutation, Phosphatidylinositol 3-Kinases, Prognosis, Protein Kinase Inhibitors, Proteomics, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-met, Signal Transduction, Stromal Cells, Sulfonamides, Tumor Microenvironment, Vemurafenib, General Science & Technology
Abstract

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.

Published
2012

16. Data from Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

Author

Seashore-Ludlow, Brinton, primary, Rees, Matthew G., primary, Cheah, Jaime H., primary, Cokol, Murat, primary, Price, Edmund V., primary, Coletti, Matthew E., primary, Jones, Victor, primary, Bodycombe, Nicole E., primary, Soule, Christian K., primary, Gould, Joshua, primary, Alexander, Benjamin, primary, Li, Ava, primary, Montgomery, Philip, primary, Wawer, Mathias J., primary, Kuru, Nurdan, primary, Kotz, Joanne D., primary, Hon, C. Suk-Yee, primary, Munoz, Benito, primary, Liefeld, Ted, primary, Dančík, Vlado, primary, Bittker, Joshua A., primary, Palmer, Michelle, primary, Bradner, James E., primary, Shamji, Alykhan F., primary, Clemons, Paul A., primary, and Schreiber, Stuart L., primary

Published
2023
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17. Supplmental Figures S1 - S8 from Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

Author

Seashore-Ludlow, Brinton, primary, Rees, Matthew G., primary, Cheah, Jaime H., primary, Cokol, Murat, primary, Price, Edmund V., primary, Coletti, Matthew E., primary, Jones, Victor, primary, Bodycombe, Nicole E., primary, Soule, Christian K., primary, Gould, Joshua, primary, Alexander, Benjamin, primary, Li, Ava, primary, Montgomery, Philip, primary, Wawer, Mathias J., primary, Kuru, Nurdan, primary, Kotz, Joanne D., primary, Hon, C. Suk-Yee, primary, Munoz, Benito, primary, Liefeld, Ted, primary, Dančík, Vlado, primary, Bittker, Joshua A., primary, Palmer, Michelle, primary, Bradner, James E., primary, Shamji, Alykhan F., primary, Clemons, Paul A., primary, and Schreiber, Stuart L., primary

Published
2023
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18. Supplemental Tables S1 - S7 from Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

Author

Seashore-Ludlow, Brinton, primary, Rees, Matthew G., primary, Cheah, Jaime H., primary, Cokol, Murat, primary, Price, Edmund V., primary, Coletti, Matthew E., primary, Jones, Victor, primary, Bodycombe, Nicole E., primary, Soule, Christian K., primary, Gould, Joshua, primary, Alexander, Benjamin, primary, Li, Ava, primary, Montgomery, Philip, primary, Wawer, Mathias J., primary, Kuru, Nurdan, primary, Kotz, Joanne D., primary, Hon, C. Suk-Yee, primary, Munoz, Benito, primary, Liefeld, Ted, primary, Dančík, Vlado, primary, Bittker, Joshua A., primary, Palmer, Michelle, primary, Bradner, James E., primary, Shamji, Alykhan F., primary, Clemons, Paul A., primary, and Schreiber, Stuart L., primary

Published
2023
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19. Supplementary Methods, Figure Legends, Tables S8 - S11 from Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

Author

Seashore-Ludlow, Brinton, primary, Rees, Matthew G., primary, Cheah, Jaime H., primary, Cokol, Murat, primary, Price, Edmund V., primary, Coletti, Matthew E., primary, Jones, Victor, primary, Bodycombe, Nicole E., primary, Soule, Christian K., primary, Gould, Joshua, primary, Alexander, Benjamin, primary, Li, Ava, primary, Montgomery, Philip, primary, Wawer, Mathias J., primary, Kuru, Nurdan, primary, Kotz, Joanne D., primary, Hon, C. Suk-Yee, primary, Munoz, Benito, primary, Liefeld, Ted, primary, Dančík, Vlado, primary, Bittker, Joshua A., primary, Palmer, Michelle, primary, Bradner, James E., primary, Shamji, Alykhan F., primary, Clemons, Paul A., primary, and Schreiber, Stuart L., primary

Published
2023
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20. A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

Author

Yao, Zizhen, primary, van Velthoven, Cindy T. J., additional, Kunst, Michael, additional, Zhang, Meng, additional, McMillen, Delissa, additional, Lee, Changkyu, additional, Jung, Won, additional, Goldy, Jeff, additional, Abdelhak, Aliya, additional, Baker, Pamela, additional, Barkan, Eliza, additional, Bertagnolli, Darren, additional, Campos, Jazmin, additional, Carey, Daniel, additional, Casper, Tamara, additional, Chakka, Anish Bhaswanth, additional, Chakrabarty, Rushil, additional, Chavan, Sakshi, additional, Chen, Min, additional, Clark, Michael, additional, Close, Jennie, additional, Crichton, Kirsten, additional, Daniel, Scott, additional, Dolbeare, Tim, additional, Ellingwood, Lauren, additional, Gee, James, additional, Glandon, Alexandra, additional, Gloe, Jessica, additional, Gould, Joshua, additional, Gray, James, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Hirschstein, Daniel, additional, Ho, Windy, additional, Jin, Kelly, additional, Kroll, Matthew, additional, Lathia, Kanan, additional, Leon, Arielle, additional, Long, Brian, additional, Maltzer, Zoe, additional, Martin, Naomi, additional, McCue, Rachel, additional, Meyerdierks, Emma, additional, Nguyen, Thuc Nghi, additional, Pham, Trangthanh, additional, Rimorin, Christine, additional, Ruiz, Augustin, additional, Shapovalova, Nadiya, additional, Slaughterbeck, Cliff, additional, Sulc, Josef, additional, Tieu, Michael, additional, Torkelson, Amy, additional, Tung, Herman, additional, Cuevas, Nasmil Valera, additional, Wadhwani, Katherine, additional, Ward, Katelyn, additional, Levi, Boaz, additional, Farrell, Colin, additional, Thompson, Carol L., additional, Mufti, Shoaib, additional, Pagan, Chelsea M., additional, Kruse, Lauren, additional, Dee, Nick, additional, Sunkin, Susan M., additional, Esposito, Luke, additional, Hawrylycz, Michael J., additional, Waters, Jack, additional, Ng, Lydia, additional, Smith, Kimberly A., additional, Tasic, Bosiljka, additional, Zhuang, Xiaowei, additional, and Zeng, Hongkui, additional

Published
2023
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21. Author Correction: A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors

Author

Slyper, Michal, Porter, Caroline B. M., Ashenberg, Orr, Waldman, Julia, Drokhlyansky, Eugene, Wakiro, Isaac, Smillie, Christopher, Smith-Rosario, Gabriela, Wu, Jingyi, Dionne, Danielle, Vigneau, Sébastien, Jané-Valbuena, Judit, Tickle, Timothy L., Napolitano, Sara, Su, Mei-Ju, Patel, Anand G., Karlstrom, Asa, Gritsch, Simon, Nomura, Masashi, Waghray, Avinash, Gohil, Satyen H., Tsankov, Alexander M., Jerby-Arnon, Livnat, Cohen, Ofir, Klughammer, Johanna, Rosen, Yanay, Gould, Joshua, Nguyen, Lan, Hofree, Matan, Tramontozzi, Peter J., Li, Bo, Wu, Catherine J., Izar, Benjamin, Haq, Rizwan, Hodi, F. Stephen, Yoon, Charles H., Hata, Aaron N., Baker, Suzanne J., Suvà, Mario L., Bueno, Raphael, Stover, Elizabeth H., Clay, Michael R., Dyer, Michael A., Collins, Natalie B., Matulonis, Ursula A., Wagle, Nikhil, Johnson, Bruce E., Rotem, Asaf, Rozenblatt-Rosen, Orit, and Regev, Aviv

Published
2020
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22. Targeting MTHFD2 in acute myeloid leukemia

Author

Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Puissant, Alexandre, Lewis, Caroline, Ramos, Azucena, Hemann, Michael, Vander Heiden, Matthew G., Pikman, Yana, Alexe, Gabriela, Furman, Andrew, Chen, Liying M., Frumm, Stacey M., Ross, Linda, Fenouille, Nina, Bassil, Christopher F., Gould, Joshua, Stone, Richard M., DeAngelo, Daniel J., Galinsky, Ilene, Clish, Clary B., Kung, Andrew L., Banerji, Versha, Stegmaier, Kimberly, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Puissant, Alexandre, Lewis, Caroline, Ramos, Azucena, Hemann, Michael, Vander Heiden, Matthew G., Pikman, Yana, Alexe, Gabriela, Furman, Andrew, Chen, Liying M., Frumm, Stacey M., Ross, Linda, Fenouille, Nina, Bassil, Christopher F., Gould, Joshua, Stone, Richard M., DeAngelo, Daniel J., Galinsky, Ilene, Clish, Clary B., Kung, Andrew L., Banerji, Versha, and Stegmaier, Kimberly

Abstract

Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. It has been known for decades that cancer cells have an altered metabolism. As early as the 1920s, Otto Warburg observed that tumor cells consume glucose at a high rate and undergo fermentation even in the presence of oxygen (Warburg et al., 1927). Since then, drugs targeting metabolism have transformed the treatment of certain cancers. In the 1940s, the discovery and application of aminopterin, which was later found to target dihydrofolate reductase (DHFR), a cytoplasmic enzyme involved in one-carbon folate metabolism, yielded the first remission in a child with acute lymphoblastic leukemia (Farber et al., 1948). Other folate derivatives, such as methotrexate, were later developed. More recently, drugs such as 5-fluorouracil and pemetrexed that target thymidylate synthetase, another enzyme involved in one-carbon folate metabolism, were found to be effective therapies for some cancers (Locasale, 2013). The discovery of germline and somatic mutations that alter metabolic proteins in cancer further supports the role of, National Cancer Institute (U.S.) (R01 CA140292), National Cancer Institute (U.S.) (R21 CA198028), National Heart, Lung, and Blood Institute (5T32 HL07574-32), Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (5K12HD052896-09), Library of Integrated Cellular Signatures (U54HG006093), Library of Integrated Cellular Signatures (U54HL127366)

Published
2022

23. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

Author

Lohr, Jens G., Stojanov, Petar, Lawrence, Michael S., Auclair, Daniel, Chapuy, Bjoern, Sougnez, Carrie, Cruz-Gordillo, Peter, Knoechel, Birgit, Asmann, Yan W., Slager, Susan L., Novak, Anne J., Dogan, Ahmet, Ansell, Stephen M., Link, Brian K., Zou, Lihua, Gould, Joshua, Saksena, Gordon, Stransky, Nicolas, Rangel-Escareño, Claudia, Fernandez-Lopez, Juan Carlos, Hidalgo-Miranda, Alfredo, Melendez-Zajgla, Jorge, Hernández-Lemus, Enrique, Schwarz-Cruz y Celis, Angela, Imaz-Rosshandler, Ivan, Ojesina, Akinyemi I., Jung, Joonil, Pedamallu, Chandra S., Lander, Eric S., Habermann, Thomas M., Cerhan, James R., Shipp, Margaret A., Getz, Gad, and Golub, Todd R.

Published
2012

24. STOmicsDB: a database of Spatial Transcriptomic data

Author

Xu, Zhicheng, primary, Wang, Weiwen, additional, Yang, Tao, additional, Chen, Jing, additional, Huang, Yan, additional, Gould, Joshua, additional, Du, Wensi, additional, Yang, Fan, additional, Li, Ling, additional, Lai, Tingting, additional, Hua, Cong, additional, Hu, Shoujie, additional, Cai, Jia, additional, Li, Honge, additional, You, Lijin, additional, Zeng, Wenjun, additional, Wang, Bo, additional, Liu, Longqi, additional, Xu, Xun, additional, Chen, Fengzhen, additional, and Wei, Xiaofeng, additional

Published
2022
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25. Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer

Author

Cheung, Hiu Wing, Cowley, Glenn S., Weir, Barbara A., Boehm, Jesse S., Rusin, Scott, Scott, Justine A., East, Alexandra, Ali, Levi D., Lizotte, Patrick H., Wong, Terence C., Jiang, Guozhi, Hsiao, Jessica, Mermel, Craig H., Getz, Gad, Barretina, Jordi, Gopal, Shuba, Tamayo, Pablo, Gould, Joshua, Tsherniak, Aviad, Stransky, Nicolas, Luo, Biao, Ren, Yin, Drapkin, Ronny, Bhatia, Sangeeta N., Mesirov, Jill P., Garraway, Levi A., Meyerson, Matthew, Lander, Eric S., Root, David E., and Hahn, William C.

Published
2011

26. Cumulus provides cloud-based data analysis for large-scale single-cell and single-nucleus RNA-seq

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Li, Bo, Gould, Joshua, Yang, Yiming, Sarkizova, Siranush, Tabaka, Marcin, Ashenberg, Orr, Rosen, Yanay, Slyper, Michal, Kowalczyk, Monika S, Villani, Alexandra-Chloé, Tickle, Timothy, Hacohen, Nir, Rozenblatt-Rosen, Orit, Regev, Aviv, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Li, Bo, Gould, Joshua, Yang, Yiming, Sarkizova, Siranush, Tabaka, Marcin, Ashenberg, Orr, Rosen, Yanay, Slyper, Michal, Kowalczyk, Monika S, Villani, Alexandra-Chloé, Tickle, Timothy, Hacohen, Nir, Rozenblatt-Rosen, Orit, and Regev, Aviv

Abstract

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Massively parallel single-cell and single-nucleus RNA sequencing has opened the way to systematic tissue atlases in health and disease, but as the scale of data generation is growing, so is the need for computational pipelines for scaled analysis. Here we developed Cumulus—a cloud-based framework for analyzing large-scale single-cell and single-nucleus RNA sequencing datasets. Cumulus combines the power of cloud computing with improvements in algorithm and implementation to achieve high scalability, low cost, user-friendliness and integrated support for a comprehensive set of features. We benchmark Cumulus on the Human Cell Atlas Census of Immune Cells dataset of bone marrow cells and show that it substantially improves efficiency over conventional frameworks, while maintaining or improving the quality of results, enabling large-scale studies.

Published
2021

27. A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2

Author

Delorey, Toni M., primary, Ziegler, Carly G. K., additional, Heimberg, Graham, additional, Normand, Rachelly, additional, Yang, Yiming, additional, Segerstolpe, Asa, additional, Abbondanza, Domenic, additional, Fleming, Stephen J., additional, Subramanian, Ayshwarya, additional, Montoro, Daniel T., additional, Jagadeesh, Karthik A., additional, Dey, Kushal K., additional, Sen, Pritha, additional, Slyper, Michal, additional, Pita-Juárez, Yered H., additional, Phillips, Devan, additional, Bloom-Ackerman, Zohar, additional, Barkas, Nick, additional, Ganna, Andrea, additional, Gomez, James, additional, Normandin, Erica, additional, Naderi, Pourya, additional, Popov, Yury V., additional, Raju, Siddharth S., additional, Niezen, Sebastian, additional, Tsai, Linus T.-Y., additional, Siddle, Katherine J., additional, Sud, Malika, additional, Tran, Victoria M., additional, Vellarikkal, Shamsudheen K., additional, Amir-Zilberstein, Liat, additional, Atri, Deepak S., additional, Beechem, Joseph, additional, Brook, Olga R., additional, Chen, Jonathan, additional, Divakar, Prajan, additional, Dorceus, Phylicia, additional, Engreitz, Jesse M., additional, Essene, Adam, additional, Fitzgerald, Donna M., additional, Fropf, Robin, additional, Gazal, Steven, additional, Gould, Joshua, additional, Grzyb, John, additional, Harvey, Tyler, additional, Hecht, Jonathan, additional, Hether, Tyler, additional, Jane-Valbuena, Judit, additional, Leney-Greene, Michael, additional, Ma, Hui, additional, McCabe, Cristin, additional, McLoughlin, Daniel E., additional, Miller, Eric M., additional, Muus, Christoph, additional, Niemi, Mari, additional, Padera, Robert, additional, Pan, Liuliu, additional, Pant, Deepti, additional, Pe’er, Carmel, additional, Pfiffner-Borges, Jenna, additional, Pinto, Christopher J., additional, Plaisted, Jacob, additional, Reeves, Jason, additional, Ross, Marty, additional, Rudy, Melissa, additional, Rueckert, Erroll H., additional, Siciliano, Michelle, additional, Sturm, Alexander, additional, Todres, Ellen, additional, Waghray, Avinash, additional, Warren, Sarah, additional, Zhang, Shuting, additional, Zollinger, Daniel R., additional, Cosimi, Lisa, additional, Gupta, Rajat M., additional, Hacohen, Nir, additional, Hide, Winston, additional, Price, Alkes L., additional, Rajagopal, Jayaraj, additional, Tata, Purushothama Rao, additional, Riedel, Stefan, additional, Szabo, Gyongyi, additional, Tickle, Timothy L., additional, Hung, Deborah, additional, Sabeti, Pardis C., additional, Novak, Richard, additional, Rogers, Robert, additional, Ingber, Donald E., additional, Gordon Jiang, Z., additional, Juric, Dejan, additional, Babadi, Mehrtash, additional, Farhi, Samouil L., additional, Stone, James R., additional, Vlachos, Ioannis S., additional, Solomon, Isaac H., additional, Ashenberg, Orr, additional, Porter, Caroline B.M., additional, Li, Bo, additional, Shalek, Alex K., additional, Villani, Alexandra-Chloé, additional, Rozenblatt-Rosen, Orit, additional, and Regev, Aviv, additional

Published
2021
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28. A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations

Author

Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Litichevskiy, Lev, Peckner, Ryan, Abelin, Jennifer G., Asiedu, Jacob K., Creech, Amanda L., Davis, John F., Davison, Desiree, Dunning, Caitlin M., Egertson, Jarrett D., Egri, Shawn, Gould, Joshua, Ko, Tak, Johnson, Sarah A., Lahr, David L., Lam, Daniel, Liu, Zihan, MacLean, Brendan X., Lyons, Nicholas J., Lu, Xiaodong, Mungenast, Alison, Officer, Adam, Natoli, Ted E., Papanastasiou, Malvina, Patel, Jinal, Sharma, Vagisha, Toder, Courtney, Tubelli, Andrew A., Young, Jennie Zin-Ney, Carr, Steven A, Golub, Todd, Subramanian, Aravind, MacCoss, Michael J., Tsai, Li-Huei, Jaffe, Jacob D., Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Litichevskiy, Lev, Peckner, Ryan, Abelin, Jennifer G., Asiedu, Jacob K., Creech, Amanda L., Davis, John F., Davison, Desiree, Dunning, Caitlin M., Egertson, Jarrett D., Egri, Shawn, Gould, Joshua, Ko, Tak, Johnson, Sarah A., Lahr, David L., Lam, Daniel, Liu, Zihan, MacLean, Brendan X., Lyons, Nicholas J., Lu, Xiaodong, Mungenast, Alison, Officer, Adam, Natoli, Ted E., Papanastasiou, Malvina, Patel, Jinal, Sharma, Vagisha, Toder, Courtney, Tubelli, Andrew A., Young, Jennie Zin-Ney, Carr, Steven A, Golub, Todd, Subramanian, Aravind, MacCoss, Michael J., Tsai, Li-Huei, and Jaffe, Jacob D.

Abstract

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the “connectivity” framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics. A large compendium of cellular responses to drugs as profiled through proteomic assays of phosphosignaling and histone modifications reveals cellular responses that transcend lineage, discovers unexpected associations between drugs, and recognizes therapeutic hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. Keywords: mass spectrometry; proteomics; drug discovery; signaling; epigenetics; mechanism of action; LINCS project; GCP; P100; L1000, NIH Common Fund's Library of Integrated Network-based Cellular Signatures (LINCS) program (Grant U54HG008097), NIH Common Fund's Library of Integrated Network-based Cellular Signatures (LINCS) program (Grant U54HG008699)

Published
2020

29. A Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seq

Author

Boroughs, Angela C., primary, Larson, Rebecca C., additional, Marjanovic, Nemanja D., additional, Gosik, Kirk, additional, Castano, Ana P., additional, Porter, Caroline B.M., additional, Lorrey, Selena J., additional, Ashenberg, Orr, additional, Jerby, Livnat, additional, Hofree, Matan, additional, Smith-Rosario, Gabriela, additional, Morris, Robert, additional, Gould, Joshua, additional, Riley, Lauren S., additional, Berger, Trisha R., additional, Riesenfeld, Samantha J., additional, Rozenblatt-Rosen, Orit, additional, Choi, Bryan D., additional, Regev, Aviv, additional, and Maus, Marcela V., additional

Published
2020
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30. List of Contributors

Author

Abad, Juan-Carlos, primary, Abelson, Mark B, additional, Abramson, David H, additional, Acquadro, Martin A, additional, Adamis, Anthony P, additional, Adams, Wesley H, additional, Afshari, Natalie A, additional, Ai, Everett, additional, Aiello, Lloyd M, additional, Aiello, Lloyd P, additional, Akduman, Levent, additional, Albano, Marissa L, additional, Albert, Daniel M., additional, Alexandrou, Terry J, additional, Alfonso, Eduardo C, additional, Alié, Jorge L, additional, Alizadeh, Hassan, additional, Al Jadaan, Ibrahim A, additional, Al-Jastaneiah, Sabah, additional, Allen, Calliope E, additional, Allen, David, additional, Allen, Robert C, additional, Alm, Albert, additional, Al-Swailem, Samar, additional, Alt, Abigail K, additional, Altaweel, Michael M, additional, Anderson, Russell, additional, Andreoli, Christopher M, additional, Androudi, Sofia, additional, Ang, Leonard PK, additional, Anzaar, Fahd, additional, Apple, David J, additional, Arrigg, Claudia A, additional, Artal, Pablo, additional, Asbell, Penny, additional, Asdourian, George K, additional, Atebara, Neal, additional, Atmaca-Sonmez, Pelin, additional, Audo, Isabelle, additional, Auffarth, Gerd U, additional, Avery, Robin K, additional, Azar, Dimitri T, additional, Baker, Ann S, additional, Balles, Mark, additional, Barnes, Scott D, additional, Barnett, Donald M, additional, Barney, Neal P, additional, Barouch, Fina C, additional, Bartley, George B, additional, Barton, Jason JS, additional, Behlau, Irmgard, additional, Belda, Jose I, additional, Bennett, Jeffrey L, additional, Bennett, Timothy J, additional, Berdy, Gregg J, additional, Bernardino, Carlo Roberto, additional, Bernardino, Vitaliano, additional, Berson, Eliot L, additional, Bharadwaj, Amitabh, additional, Bhisitkul, Robert, additional, Bhui, Ravinder D, additional, Bilyk, Jurij, additional, Biousse, Valérie, additional, Bird, Alan C, additional, Blair, Norman Paul, additional, Blodi, Barbara A, additional, Blumenkranz, Mark S, additional, Boldt, H Culver, additional, Borchert, Mark S, additional, Borrillo, Luigi, additional, Borodic, Gary E, additional, Boruchoff, S Arthur, additional, Bose, Swaraj, additional, Boulton, Michael E, additional, Bowman, RW, additional, Bradley, Elizabeth A, additional, Brazitikos, Periklis D, additional, Breeze, Robert, additional, Bressler, Neil M, additional, Bressler, Susan B, additional, Brini, Alfred, additional, Budenz, Donald L, additional, Buffenn, Angela N, additional, Burk, Scott E, additional, Butrus, Salim, additional, Callanan, David, additional, Cameron, J Douglas, additional, Cantor, Louis B, additional, Cantore, William A, additional, Cantu-Dibildox, Jorge, additional, Casas, Victoria, additional, Casper, Miriam, additional, Casten, Robin J, additional, Catoira, Yara P, additional, Cavallerano, Jerry, additional, Chai, Samantha J, additional, Chalita, Maria R, additional, Chamberlain, Sherman M, additional, Chan, Audrey S, additional, Chan, Chi-Chao, additional, Chan, Paul, additional, Chapin, Matthew J, additional, Chapman, Karen L, additional, Chen, Eric, additional, Chen, Joe, additional, Chen, Julie A, additional, Chen, Teresa C, additional, Chen, Zhou, additional, Chévez-Barrios, Patricia, additional, Chew, Emily Y, additional, Chiang, Mark, additional, Chodosh, James, additional, Chong, Eva-Marie, additional, Chun, Denise, additional, Chylack, Leo T, additional, Ciardella, Antonio P, additional, Civan, Mortimer, additional, Clamen, Liane, additional, Clark, John I, additional, Cockerham, Glenn, additional, Cohen, Andre, additional, Cohen, Elisabeth J, additional, Colby, Kathryn A, additional, Coleman, Anne L, additional, Coleman, Hanna R, additional, Colin, Joseph, additional, Collier, J Michael, additional, Comer, Grant M, additional, Conlon, M Ronan, additional, Cooper, Kim E, additional, Corbett, James J, additional, Coma, Miguel C, additional, Cyrlin, Marshall N, additional, Dagi, Linda R, additional, Dahlgren, Matthew A, additional, Daley, Timothy J, additional, Da Mata, Andrea P, additional, Damato, Bertil, additional, D'Amico, Donald J, additional, Dana, Reza, additional, Danan-Husson, Aude, additional, Danesh-Meyer, Helen B, additional, Danis, Ronald P, additional, Darlington, Jason K, additional, Davidson, Stefanie L, additional, Davis, Janet L, additional, Davis, Elizabeth A, additional, de la Cruz, Jose J, additional, de la Garza, Adam G, additional, DeAngelis, Margaret M, additional, DeMartelaere, Sheri L, additional, Demer, Joseph L, additional, Dhaliwal, Avninder, additional, Dieckert, J Paul, additional, Do, Diana V, additional, Doane, Marshall G, additional, Dodds, Christopher, additional, Dohlman, Claes H, additional, Donati, Guy, additional, Donnenfeld, Eric D, additional, Drack, Arlene, additional, Dryja, Thaddeus P, additional, Dueker, David, additional, Duker, Jay S, additional, Dunbar, Jennifer A, additional, Dunn, James P, additional, Dupps, William J, additional, Durand, Marlene L, additional, Dutton, Jonathan J, additional, Eandi, Chiara M, additional, Edward, Deepak P, additional, Egan, Robert A, additional, Eichenbaum, David A, additional, Eklund, Susan E, additional, Engle, Elizabeth C, additional, Erickson, Kristine, additional, Esmaeli, Bita, additional, Fay, Aaron, additional, Feiner, Leonard, additional, Fekrat, Sharon, additional, Ferris, Frederick L, additional, Fine, Howard F, additional, Fletcher, Donald C, additional, Flikier, Paul, additional, Floyd, Richard P, additional, Flynn, Harry W, additional, Fong, Donald S, additional, Font, Ramon L, additional, Forbes, Brian JR, additional, Foroozan, Rod, additional, Foster, Bradley S, additional, Foster, C Stephen, additional, Foster, Jill A, additional, Foulks, Gary N, additional, Fountain, Tamara R, additional, Fox, Gregory M, additional, Freddo, Thomas F, additional, Freedman, Sharon F, additional, Freund, K Bailey, additional, Friberg, Thomas R, additional, Friedman, Alan H, additional, Friedman, David, additional, Friedman, Deborah I, additional, Friedman, Ephraim, additional, Fu, Arthur D, additional, Fulton, Anne B, additional, Galal, Ahmed, additional, Galetta, Steven, additional, Gallardo, Mark, additional, Gallie, Brenda, additional, Garner, Alec, additional, Garrity, James A, additional, Gatinel, Damien, additional, Gedde, Steven J, additional, Geist, Craig E, additional, Gerber, Steve, additional, Ghanem, Ramon C, additional, Gieser, Jon P, additional, Gilmore, Michael S, additional, Gimbel, Howard V, additional, Gipson, Ilene K, additional, Glover, Tyrone, additional, Goldberg, Robert A, additional, Goldenfeld, Mordechai, additional, Goldstein, Scott M, additional, Gomi, Cintia F, additional, Gong, Haiyan, additional, Gonzales, John A, additional, Goosey, John, additional, Gottlieb, Justin L, additional, Gould, Joshua, additional, Gragoudas, Evangelos S, additional, Granet, David B, additional, Greaney, Michael J, additional, Green, Daniel G, additional, Grehn, Franz, additional, Greiner, Jack V, additional, Greven, Craig M, additional, Griepentrog, Gregory J, additional, Groenewald, Carl, additional, Grosskreutz, Cynthia L, additional, Grover, Lori Latowski, additional, Gullapalli, Vamsi K, additional, Gulur, Padma, additional, Gunther, Jonathan, additional, Gupta, Manish, additional, Gupta, Mayank, additional, Guyer, David R, additional, Haivala, Darin R, additional, Haller, Julia A, additional, Halmagyi, GM, additional, Halperin, Lawrence S, additional, Hamdi, Islam M, additional, Hamilton, Steven R, additional, Hammersmith, Kristin M, additional, Han, Dennis P, additional, Hansen, Ronald M, additional, Harbour, J William, additional, Hariprasad, Seenu M, additional, Harissi-Dagher, Mona, additional, Hassan, Shirin E., additional, Hatton, Mark P, additional, Hawley, Pamela, additional, Hayashida, Yasutaka, additional, Heckenlively, John R, additional, Hedges, Thomas R, additional, Heggie, Alfred D, additional, Heher, Katrinka L, additional, Heier, Jeffrey S, additional, Hejtmancik, J Fielding, additional, Henderson, Bonnie A, additional, Hersh, Peter S, additional, Hidayat, Ahmed A, additional, Higginbotham, Eva Juliet, additional, Hirose, Tatsuo, additional, Ho, Allen C, additional, Ho, ThucAnh T, additional, Hogan, R Nick, additional, Holck, David E, additional, Holekamp, Nancy M, additional, Hovland, Peter G, additional, Hsu, Thomas C, additional, Hsu, William C, additional, Huang, Andrew JW, additional, Hughes, Mark S, additional, Hui, Jennifer, additional, Hunter, David G, additional, Huryn, Laryssa A, additional, Husain, Deeba, additional, Hyndiuk, Robert A, additional, Ip, Michael, additional, Jacobs, Brian J, additional, Jakobiec, Frederick A, additional, Jampol, Lee M, additional, Jensen, Harold G, additional, Ji, Fei, additional, Johnson, David L, additional, Johnson, Douglas H, additional, Johnson, Mark W, additional, Johnson, R Paul, additional, Johnson, Robert N, additional, Joos, Karen M, additional, Joyce, Nancy C, additional, Jumper, J Michael, additional, Jurkunas, Ula V., additional, Kahana, Alon, additional, Kahook, Malik Y, additional, Kanner, Elliott, additional, Kalwerisky, Kevin, additional, Kaplan, Henry J, additional, Karatza, Ekaterini C, additional, Kardon, Randy, additional, Katowitz, James A, additional, Katowitz, William R, additional, Kazlas, Melanie, additional, Keefe, Kelly S, additional, Kelley, Lara, additional, Kent, Charles J, additional, Kenyon, Kenneth R, additional, Khan, Bilal F, additional, Khan, Jemshed A, additional, Khan, Naheed W, additional, Khaw, Peng Tee, additional, Kherani, Femida, additional, Kim, Eva C, additional, Kim, Hee Joon, additional, Kim, Ivana K, additional, Kim, Jonathan W, additional, Kim, Rosa Y, additional, Kim, Stella K, additional, Kim, Tae-Im, additional, Klais, Christina M, additional, Klapper, Stephen R, additional, Klein, Barbara EK, additional, Kleinmann, Guy, additional, Klink, Thomas, additional, Klisovic, Dino D, additional, Klyce, Stephen D, additional, Kocaturk, Tolga, additional, Kohnen, Thomas, additional, Kojima, Takeshi, additional, Koller, Tobias, additional, Kostick, David A, additional, Kraut, Joel A, additional, Krishnan, Chandrasekharan, additional, Krueger, Ronald R, additional, Krug, Joseph H, additional, Krupsky, Sara, additional, Kuchtey, Rachel W, additional, Kurban, Ramsay S, additional, Kurz, Paul A, additional, Kuszak, JR, additional, Kwon, Young H, additional, Labbe, Thad A, additional, Lam, Deborah L, additional, Lamkin, Jeffrey C, additional, Lamping, Kathleen A, additional, Lane, Anne Marie, additional, Lane, Katherine A, additional, Lane, Keith J, additional, Lass, Jonathan H, additional, Lawrence, Mary G, additional, Lee, Andrew G, additional, Lee, Carol M, additional, Lee, Michael S, additional, Lee, Paul P, additional, Lee, William B, additional, Leibovitch, Igal, additional, Lemke, Bradley N, additional, Lemley, Craig A, additional, Leonardi, Andrea, additional, Lessell, Simmons, additional, Levin, Leonard A, additional, Levy-Clarke, Grace A, additional, Lew, Julie C, additional, Lewis, Craig, additional, Li, Wei, additional, Lim, Laurence S, additional, Lim, Lyndell L, additional, Lim, Wee-Kiak, additional, Liu, Grant T, additional, Loewenstein, John I, additional, Lott, McGregor N, additional, Lowry, Jonathan C, additional, Lyon, David B, additional, Lytle, Robert E, additional, MacCumber, Mathew, additional, Mackool, Bonnie T, additional, Madiwale, Nalini A, additional, Mah, Francis, additional, Mainster, Martin A, additional, Manning, Michael H, additional, Mansberger, Steven L, additional, Marc, Robert E, additional, Marchong, Mellone, additional, Marcus, Dennis M, additional, Mares, Julie A, additional, Marr, Brian P, additional, Martinez, Carlos E, additional, Massof, Robert W, additional, Matsumoto, Yukihiro, additional, Mattox, Cynthia, additional, Maus, Marlon, additional, McCabe, Cathleen M, additional, McCormick, Steven A, additional, McCrakken, Michael, additional, McCulley, James P, additional, McDermott, John A, additional, McDonald, H Richard, additional, McDonald, Marguerite B, additional, McDonnell, Peter J, additional, McGillivray, Robert, additional, McKeown, Craig A, additional, McLaughlin, James, additional, McMullen, W Wynn, additional, Melamed, Shlomo, additional, Meligonis, George, additional, Mendrinos, Efstratios, additional, Meyer, Dale R, additional, Meyerle, Catherine B, additional, Mieler, William F, additional, Migliori, Michael, additional, Mihm, Martin C, additional, Miller, Darlene, additional, Miller, David, additional, Miller, Joan W, additional, Miller, Neil R, additional, Mills, David M, additional, Mills, Monte D, additional, Milman, Tatyana, additional, Mogk, Lylas, additional, Mogk, Marja, additional, Monés, Jordi, additional, Montes-Micó, Robert, additional, Morse, Christie L, additional, Morton, Asa D, additional, Moskowitz, Anne, additional, Mukai, Shizuo, additional, Murphree, A Linn, additional, Murphy, Robert P, additional, Murray, Timothy G, additional, Murray, Philip I, additional, Nagao, Karina, additional, Neitz, Jay, additional, Neitz, Maureen, additional, Netland, Peter A, additional, Neufeld, Arthur H, additional, Newman, Nancy J, additional, Ng, Eugene WM, additional, Nguyen, Quan Dong, additional, Niederkorn, Jerry Y, additional, Noecker, Robert J, additional, Nussenblatt, Robert B, additional, O'Brien, Joan M, additional, O'Brien, Paul D, additional, O'Brien, Terrence P, additional, O'Day, Denis, additional, Olk, R Joseph, additional, Olsen, Karl R, additional, Onal, Sumru, additional, Ooi, Yen Hoong, additional, Opremcak, E Mitchel, additional, Ousler, George, additional, Ozment, Randall R, additional, Packer, Samuel, additional, Palmer, Millicent L, additional, Papaliodis, George N, additional, Park, DJ John, additional, Parke, David W, additional, Parsa, Cameron F, additional, Parsons, M Andrew, additional, Pasquale, Louis R, additional, Patel, Neha N, additional, Patel, Sayjal J, additional, Patrianakos, Thomas D, additional, Patrinely, James R, additional, Pavan-Langston, Deborah, additional, Peli, Eli, additional, Pepin, Susan M, additional, Perez, Victor L, additional, Pérez-Santonja, Juan J, additional, Perfect, John R, additional, Perry, Henry D, additional, Piatigorsky, Joram, additional, Pieramici, Dante, additional, Pierce, Eric A, additional, Pineda, Roberto, additional, Pless, Misha L, additional, Pomeranz, Howard D, additional, Pournaras, Constantin J, additional, Power, William, additional, Prakash, Manvi, additional, Prasad, Anita G, additional, Purvin, Valerie, additional, Quillen, David A, additional, Quinn, Graham E, additional, Rabena, Melvin D, additional, Rae, James L, additional, Raizman, Michael B, additional, Randazzo, Alessandro, additional, Rao, Narsing A, additional, Rapuano, Christopher J, additional, Reeves, Sherman W, additional, Regillo, Carl D, additional, Reichel, Elias, additional, Reinke, Martin H, additional, Rhee, Douglas, additional, Richter, Claudia U, additional, Rizzo, Joseph F, additional, Robb, Richard M, additional, Roden, Anja C, additional, Rodgers, I Rand, additional, Rodrigues, Merlyn M, additional, Ron, Yonina, additional, Rose, Geoffrey E, additional, Rosen, Emanuel S, additional, Rosenbaum, James T, additional, Rosenthal, Perry, additional, Rouse, Strutha C, additional, Rovner, Barry W, additional, Rozanowska, Malgorzata, additional, Rubin, Michael P, additional, Rubin, Peter AD, additional, Rumelt, Shimon, additional, Rustgi, Anil K, additional, Rutar, Tina, additional, Ruttum, Mark S, additional, Rutzen, Allan R, additional, Ryan, Edward T, additional, Sadun, Alfredo A, additional, Sahel, José-Alain, additional, Saligan, Leorey, additional, Salim, Sarwat, additional, Salmon, John F, additional, Salomão, Diva R, additional, Sami, David, additional, Sandberg, Michael A, additional, Sangwan, Virender S, additional, Saornil, Maria A, additional, Sassani, Joseph W, additional, Sayegh, Rony R, additional, Schachat, Andrew P, additional, Schell, Wiley A, additional, Schefler, Amy C, additional, Scheufele, Tina, additional, Schiedler, Vivian, additional, Schneider, Gretchen, additional, Schroeder, Alison, additional, Schuchard, Ronald A, additional, Schuman, Joel S, additional, Schwab, Ivan R, additional, Scott, Adrienne, additional, Scott, Ingrid U, additional, Sears, Marvin L, additional, Seddon, Johanna M, additional, Seiler, Theo, additional, Selkin, Robert P, additional, Semba, Richard D, additional, Serbanescu, Irina, additional, Sexton, Briar, additional, Shaarawy, Tarek M, additional, Shah, Peter, additional, Shapiro, Aron, additional, Sharma, Savitri, additional, Shein, Jean, additional, Shetlar, Debra J, additional, Shields, M Bruce, additional, Shields, Carol L, additional, Shields, Jerry A, additional, Shingleton, Bradford J, additional, Shore, John W, additional, Shuba, Lesya M, additional, Simon, Guy J Ben, additional, Simmons, Richard J, additional, Simpson, Michael, additional, Singh, Arun D, additional, Singh, Omah S, additional, Sisley, Karen, additional, Sit, Arthur J, additional, Smerdon, David, additional, Smiddy, William E, additional, Smith, Ronald E, additional, Smith, Terry J, additional, Snebold, Neal G, additional, Sobrin, Lucia, additional, Sorenson, John A, additional, Soukiasian, Sarkis H, additional, Spaeth, George L, additional, Spaide, Richard F, additional, Srivastava, Monika, additional, Srivastava, Sunil K, additional, Stangos, Alexandros N, additional, Starck, Tomy, additional, Stark, Walter J, additional, Stein, Joshua D, additional, Steinert, Roger F, additional, Strauss, Leon, additional, Streeten, Barbara W, additional, Streilein, J Wayne, additional, Strong, James D, additional, Sugino, Ilene K, additional, Suhler, Eric B, additional, Sullivan, Timothy J, additional, Sun, Jennifer K, additional, Sunness, Janet S, additional, Sutula, Francis C, additional, Syed, Nasreen A, additional, Ta, Christopher N, additional, Takei, Hidehiro, additional, Talamo, Jonathan H, additional, Tamesis, Richard R, additional, Tamhankar, Madhura, additional, Tarbet, Kristen J, additional, Tarver-Carr, Michelle, additional, Terry, Mark A, additional, Thomas, Joseph M, additional, Thompson, Vance, additional, Thorne, Jennifer E, additional, Thurtell, Matthew J, additional, Tingey, David P, additional, To, King W, additional, Tobaigy, Faisal M, additional, Tolentino, Michael J, additional, Tong, Melissa G, additional, Torkildsen, Gail, additional, Toth, Cynthia A, additional, Traboulsi, Elias I, additional, Trucksis, Michele, additional, Tsai, James C, additional, Tsai, Julie H, additional, Tse, David T, additional, Tseng, Scheffer CG, additional, Tu, Elmer Y, additional, Udell, Ira J, additional, Valenzuela, Alejandra A, additional, Van Gelder, Russell N, additional, Van Stavern, Gregory P, additional, Vander Veen, Deborah K, additional, Vavvas, Demetrios, additional, Verity, David H, additional, Vinciguerra, Paolo, additional, Vinger, Paul F, additional, Volpe, Nicholas J, additional, Wackernagel, Werner, additional, Wadhwa, Sonal Desai, additional, Wagoner, Michael D, additional, Waheed, Nadia K, additional, Walton, David S, additional, Wand, Martin, additional, Wang, Jie Jin, additional, Warden, Scott M, additional, Webb, Lennox, additional, Weber, David, additional, Wee, Daniel, additional, Westerfeld, Corey B, additional, Westfall, Christopher T, additional, Whitcup, Scott M, additional, White, Valerie A, additional, White, William L, additional, Wickens, Jason, additional, Wiggs, Janey L, additional, Wilensky, Jacob T, additional, Wilkinson, Charles P, additional, Williams, Patrick D, additional, Wilson, David J, additional, Wilson, M Roy, additional, Wilson, Steven E, additional, Winokur, Jules, additional, Wirostko, William J, additional, Wollstein, Gadi, additional, Wong, Albert Chak Ming, additional, Wong, Tien Y, additional, Woog, John J, additional, Wride, Michael, additional, Wu, Carolyn S, additional, WuDunn, Darrell, additional, Yang, Jean, additional, Yannuzzi, Lawrence A, additional, Yaremchuk, Michael J, additional, Yeatts, R Patrick, additional, Yee, Richard W, additional, Yeh, Steven, additional, Young, Lucy HY, additional, Yu, Jenny Y, additional, Yue, Beatrice YJT, additional, Zacks, Charles M, additional, Zagelbaum, Bruce M, additional, Zamani, Maryam, additional, Zarbin, Marco, additional, Zografos, Leonidas, additional, and Zoumalan, Christopher I, additional

Published
2008
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32. Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatment

Author

Hwang, William L., primary, Jagadeesh, Karthik A., additional, Guo, Jimmy A., additional, Hoffman, Hannah I., additional, Yadollahpour, Payman, additional, Mohan, Rahul, additional, Drokhlyansky, Eugene, additional, Van Wittenberghe, Nicholas, additional, Ashenberg, Orr, additional, Farhi, Samouil, additional, Schapiro, Denis, additional, Reeves, Jason, additional, Zollinger, Daniel R., additional, Eng, George, additional, Schenkel, Jason M., additional, Freed-Pastor, William A., additional, Rodrigues, Clifton, additional, Gould, Joshua, additional, Lambden, Conner, additional, Porter, Caroline, additional, Tsankov, Alexander, additional, Dionne, Danielle, additional, Abbondanza, Domenic, additional, Waldman, Julia, additional, Cuoco, Michael, additional, Nguyen, Lan, additional, Delorey, Toni, additional, Phillips, Devan, additional, Ciprani, Debora, additional, Kern, Marina, additional, Mehta, Arnav, additional, Fuhrman, Kit, additional, Fropf, Robin, additional, Beechem, Joseph, additional, Loeffler, Jay S., additional, Ryan, David P., additional, Weekes, Colin D., additional, Ting, David T., additional, Ferrone, Cristina R., additional, Wo, Jennifer Y., additional, Hong, Theodore S., additional, Aguirre, Andrew J., additional, Rozenblatt-Rosen, Orit, additional, Mino-Kenudson, Mari, additional, Castillo, Carlos Fernandez-del, additional, Liss, Andrew S., additional, Jacks, Tyler, additional, and Regev, Aviv, additional

Published
2020
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36. Cumulus: a cloud-based data analysis framework for large-scale single-cell and single-nucleus RNA-seq

Author

Li, Bo, primary, Gould, Joshua, additional, Yang, Yiming, additional, Sarkizova, Siranush, additional, Tabaka, Marcin, additional, Ashenberg, Orr, additional, Rosen, Yanay, additional, Slyper, Michal, additional, Kowalczyk, Monika S, additional, Villani, Alexandra-Chloé, additional, Tickle, Timothy, additional, Hacohen, Nir, additional, Rozenblatt-Rosen, Orit, additional, and Regev, Aviv, additional

Published
2019
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37. A single-cell and single-nucleus RNA-seq toolbox for fresh and frozen human tumors

Author

Slyper, Michal, primary, Porter, Caroline B. M., additional, Ashenberg, Orr, additional, Waldman, Julia, additional, Drokhlyansky, Eugene, additional, Wakiro, Isaac, additional, Smillie, Christopher, additional, Smith-Rosario, Gabriela, additional, Wu, Jingyi, additional, Dionne, Danielle, additional, Vigneau, Sébastien, additional, Jané-Valbuena, Judit, additional, Napolitano, Sara, additional, Su, Mei-Ju, additional, Patel, Anand G., additional, Karlstrom, Asa, additional, Gritsch, Simon, additional, Nomura, Masashi, additional, Waghray, Avinash, additional, Gohil, Satyen H., additional, Tsankov, Alexander M., additional, Jerby-Arnon, Livnat, additional, Cohen, Ofir, additional, Klughammer, Johanna, additional, Rosen, Yanay, additional, Gould, Joshua, additional, Li, Bo, additional, Nguyen, Lan, additional, Wu, Catherine J., additional, Izar, Benjamin, additional, Haq, Rizwan, additional, Hodi, F. Stephen, additional, Yoon, Charles H., additional, Hata, Aaron N., additional, Baker, Suzanne J., additional, Suvà, Mario L., additional, Bueno, Raphael, additional, Stover, Elizabeth H., additional, Matulonis, Ursula A., additional, Clay, Michael R., additional, Dyer, Michael A., additional, Collins, Natalie B., additional, Wagle, Nikhil, additional, Rotem, Asaf, additional, Johnson, Bruce E., additional, Rozenblatt-Rosen, Orit, additional, and Regev, Aviv, additional

Published
2019
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38. Abstract 566: Neoantigens from translated unannotated open reading frames in cancer

Author

Ouspenskaia, Tamara, primary, Law, Travis E., additional, Clauser, Karl R., additional, Klaeger, Susan, additional, Keskin, Derin B., additional, Li, Bo, additional, Christian, Elena, additional, Chow, Yuen Ting, additional, Le, Phuong M., additional, Gould, Joshua, additional, Ji, Zhe, additional, Zhang, Wandi, additional, Bachireddy, Pavan, additional, Sarkizova, Siranush, additional, Hacohen, Nir, additional, Carr, Steven A., additional, Wu, Catherine J., additional, and Regev, Aviv, additional

Published
2019
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39. Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming

Author

Schiebinger, Geoffrey, primary, Shu, Jian, additional, Tabaka, Marcin, additional, Cleary, Brian, additional, Subramanian, Vidya, additional, Solomon, Aryeh, additional, Gould, Joshua, additional, Liu, Siyan, additional, Lin, Stacie, additional, Berube, Peter, additional, Lee, Lia, additional, Chen, Jenny, additional, Brumbaugh, Justin, additional, Rigollet, Philippe, additional, Hochedlinger, Konrad, additional, Jaenisch, Rudolf, additional, Regev, Aviv, additional, and Lander, Eric S., additional

Published
2019
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40. High-density spatial transcriptomics arrays for in situ tissue profiling

Author

Vickovic, Sanja, primary, Eraslan, Gökcen, additional, Klughammer, Johanna, additional, Stenbeck, Linnea, additional, Salmén, Fredrik, additional, Äijö, Tarmo, additional, Bonneau, Richard, additional, Bergenstråhle, Ludvig, additional, Gould, Joshua, additional, Ronaghi, Mostafa, additional, Frisén, Jonas, additional, Lundeberg, Joakim, additional, Regev, Aviv, additional, and Ståhl, Patrik L, additional

Published
2019
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43. A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations

Author

Litichevskiy, Lev, primary, Peckner, Ryan, additional, Abelin, Jennifer G., additional, Asiedu, Jacob K., additional, Creech, Amanda L., additional, Davis, John F., additional, Davison, Desiree, additional, Dunning, Caitlin M., additional, Egertson, Jarrett D., additional, Egri, Shawn, additional, Gould, Joshua, additional, Ko, Tak, additional, Johnson, Sarah A., additional, Lahr, David L., additional, Lam, Daniel, additional, Liu, Zihan, additional, Lyons, Nicholas J., additional, Lu, Xiaodong, additional, MacLean, Brendan X., additional, Mungenast, Alison E., additional, Officer, Adam, additional, Natoli, Ted E., additional, Papanastasiou, Malvina, additional, Patel, Jinal, additional, Sharma, Vagisha, additional, Toder, Courtney, additional, Tubelli, Andrew A., additional, Young, Jennie Z., additional, Carr, Steven A., additional, Golub, Todd R., additional, Subramanian, Aravind, additional, MacCoss, Michael J., additional, Tsai, Li-Huei, additional, and Jaffe, Jacob D., additional

Published
2018
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45. Targeting MTHFD2 in acute myeloid leukemia

Author

Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Puissant, Alexandre, Lewis, Caroline, Ramos, Azucena, Hemann, Michael, Vander Heiden, Matthew G., Pikman, Yana, Alexe, Gabriela, Furman, Andrew, Chen, Liying M., Frumm, Stacey M., Ross, Linda, Fenouille, Nina, Bassil, Christopher F., Gould, Joshua, Stone, Richard M., DeAngelo, Daniel J., Galinsky, Ilene, Clish, Clary B., Kung, Andrew L., Banerji, Versha, Stegmaier, Kimberly, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Puissant, Alexandre, Lewis, Caroline, Ramos, Azucena, Hemann, Michael, Vander Heiden, Matthew G., Pikman, Yana, Alexe, Gabriela, Furman, Andrew, Chen, Liying M., Frumm, Stacey M., Ross, Linda, Fenouille, Nina, Bassil, Christopher F., Gould, Joshua, Stone, Richard M., DeAngelo, Daniel J., Galinsky, Ilene, Clish, Clary B., Kung, Andrew L., Banerji, Versha, and Stegmaier, Kimberly

Abstract

Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. It has been known for decades that cancer cells have an altered metabolism. As early as the 1920s, Otto Warburg observed that tumor cells consume glucose at a high rate and undergo fermentation even in the presence of oxygen (Warburg et al., 1927). Since then, drugs targeting metabolism have transformed the treatment of certain cancers. In the 1940s, the discovery and application of aminopterin, which was later found to target dihydrofolate reductase (DHFR), a cytoplasmic enzyme involved in one-carbon folate metabolism, yielded the first remission in a child with acute lymphoblastic leukemia (Farber et al., 1948). Other folate derivatives, such as methotrexate, were later developed. More recently, drugs such as 5-fluorouracil and pemetrexed that target thymidylate synthetase, another enzyme involved in one-carbon folate metabolism, were found to be effective therapies for some cancers (Locasale, 2013). The discovery of germline and somatic mutations that alter metabolic proteins in cancer further supports the role of, National Cancer Institute (U.S.) (R01 CA140292), National Cancer Institute (U.S.) (R21 CA198028), National Heart, Lung, and Blood Institute (5T32 HL07574-32), Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (5K12HD052896-09), Library of Integrated Cellular Signatures (U54HG006093), Library of Integrated Cellular Signatures (U54HL127366)

Published
2017

46. Tumor microenvironment induces innate RAF-inhibitor resistance through HGF secretion

Author

Straussman, Ravid, Morikawa, Teppei, Shee, Kevin, Barzily-Rokni, Michal, Qian, Zhi Rong, Du, Jinyan, Davis, Ashli, Mongare, Margaret M., Gould, Joshua, Frederick, Dennie T., Cooper, Zachary A., Chapman, Paul B., Solit, David B., Ribas, Antoni, Lo, Roger S., Flaherty, Keith T., Ogino, Shuji, Wargo, Jennifer A., and Golub, Todd R.

Subjects
Proto-Oncogene Proteins B-raf, Drug Resistance, Neoplasm, Hepatocyte Growth Factor, Tumor Microenvironment, Humans, Melanoma, Article
Abstract

Drug resistance remains a vexing problem in the treatment of cancer patients. While many studies have focused on cell autonomous mechanisms of drug resistance, we hypothesized that the tumor microenvironment may confer innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anti-cancer drugs. We found that stroma-mediated resistance is surprisingly common – particularly to targeted agents. We further characterized the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibition because most of these patients exhibit some degree of innate resistance1-4. Proteomic analysis showed that stromal secretion of the growth factor hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the MAPK and PI3K/AKT pathways, and immediate resistance to RAF inhibition. Immunohistochemistry confirmed stromal HGF expression in patients with BRAF-mutant melanoma and a statistically significant correlation between stromal HGF expression and innate resistance to treatment. Dual inhibition of RAF and MET resulted in reversal of drug resistance, suggesting RAF/MET combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, these studies indicate that the systematic dissection of tumor-microenvironment interactions may reveal important mechanisms underlying drug resistance.

Published
2012

47. A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations

Author

Litichevskiy, Lev, primary, Peckner, Ryan, additional, Abelin, Jennifer G., additional, Asiedu, Jacob K., additional, Creech, Amanda L., additional, Davis, John F., additional, Davison, Desiree, additional, Dunning, Caitlin M., additional, Egertson, Jarrett D., additional, Egri, Shawn, additional, Gould, Joshua, additional, Ko, Tak, additional, Johnson, Sarah A., additional, Lahr, David L., additional, Lam, Daniel, additional, Liu, Zihan, additional, Lyons, Nicholas J., additional, Lu, Xiaodong, additional, MacLean, Brendan X., additional, Mungenast, Alison E., additional, Officer, Adam, additional, Natoli, Ted E., additional, Papanastasiou, Malvina, additional, Patel, Jinal, additional, Sharma, Vagisha, additional, Toder, Courtney, additional, Tubelli, Andrew A., additional, Young, Jennie Z., additional, Carr, Steven A., additional, Golub, Todd R., additional, Subramanian, Aravind, additional, MacCoss, Michael J., additional, Tsai, Li-Huei, additional, and Jaffe, Jacob D., additional

Published
2017
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48. A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles

Author

Subramanian, Aravind, primary, Narayan, Rajiv, additional, Corsello, Steven M., additional, Peck, David D., additional, Natoli, Ted E., additional, Lu, Xiaodong, additional, Gould, Joshua, additional, Davis, John F., additional, Tubelli, Andrew A., additional, Asiedu, Jacob K., additional, Lahr, David L., additional, Hirschman, Jodi E., additional, Liu, Zihan, additional, Donahue, Melanie, additional, Julian, Bina, additional, Khan, Mariya, additional, Wadden, David, additional, Smith, Ian, additional, Lam, Daniel, additional, Liberzon, Arthur, additional, Toder, Courtney, additional, Bagul, Mukta, additional, Orzechowski, Marek, additional, Enache, Oana M., additional, Piccioni, Federica, additional, Berger, Alice H., additional, Shamji, Alykhan, additional, Brooks, Angela N., additional, Vrcic, Anita, additional, Flynn, Corey, additional, Rosains, Jacqueline, additional, Takeda, David, additional, Davison, Desiree, additional, Lamb, Justin, additional, Ardlie, Kristin, additional, Hogstrom, Larson, additional, Gray, Nathanael S., additional, Clemons, Paul A., additional, Silver, Serena, additional, Wu, Xiaoyun, additional, Zhao, Wen-Ning, additional, Read-Button, Willis, additional, Wu, Xiaohua, additional, Haggarty, Stephen J., additional, Ronco, Lucienne V., additional, Boehm, Jesse S., additional, Schreiber, Stuart L., additional, Doench, John G., additional, Bittker, Joshua A., additional, Root, David E., additional, Wong, Bang, additional, and Golub, Todd R., additional

Published
2017
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49. The Drug Repurposing Hub: a next-generation drug library and information resource

Author

Corsello, Steven M, primary, Bittker, Joshua A, additional, Liu, Zihan, additional, Gould, Joshua, additional, McCarren, Patrick, additional, Hirschman, Jodi E, additional, Johnston, Stephen E, additional, Vrcic, Anita, additional, Wong, Bang, additional, Khan, Mariya, additional, Asiedu, Jacob, additional, Narayan, Rajiv, additional, Mader, Christopher C, additional, Subramanian, Aravind, additional, and Golub, Todd R, additional

Published
2017
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50. Comprehensive Genetic Interrogation of Circulating Multiple Myeloma Cells at Single Cell Resolution

Author

Lohr, Jens G, primary, Kim, Sora, additional, Gould, Joshua, additional, Knoechel, Birgit, additional, Drier, Yotam, additional, Gray, Daniel, additional, Birrer, Nicole, additional, Wong, Bang, additional, Ha, Gavin, additional, Zhang, Cheng-Zhong, additional, Guo, Guangwu, additional, Meyerson, Matthew, additional, Yee, Andrew, additional, Boehm, Jesse, additional, Raje, Noopur, additional, and Golub, Todd R., additional

Published
2016
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