Author: "Daniel C. Rohrer" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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23 results on '"Daniel C. Rohrer"'

1. Proteogenomic Characterization of Pancreatic Ductal Adenocarcinoma

Author: Marcin J. Domagalski, Wen Jiang, Michael Smith, Li Ding, Michael Schnaubelt, Oxana Paklina, Gilbert S. Omenn, Magdalena Derejska, Karin D. Rodland, Johanna Gardner, Saravana M. Dhanasekaran, Pamela Grady, Pushpa Hariharan, David Mallery, Jesse Francis, Maciej Wiznerowicz, Eunkyung An, Nancy Roche, Ralph H. Hruban, Samuel H. Payne, Chen Huang, Olga Potapova, Gad Getz, Zhiao Shi, Shuai Guo, Oliver F. Bathe, Stacey Gabriel, Sandra Cottingham, Hui Zhang, Daniel Cui Zhou, Maureen Dyer, Houxiang Zhu, James Suh, Shuang Cai, Christopher R. Kinsinger, Felipe da Veiga Leprevost, Steven Chen, Chelsea J. Newton, Amanda G. Paulovich, Steven A. Carr, Melissa Borucki, Sandra Cerda, Troy Shelton, D. R. Mani, Tara Hiltke, Lijun Chen, Benjamin Haibe-Kains, Jiang Long, Ratna R. Thangudu, Arul M. Chinnaiyan, Mathangi Thiagarajan, Negin Vatanian, Peter Ronning, Thomas L. Bauer, Ki Sung Um, Christina Ayad, Seungyeul Yoo, Mitual Amin, Ruiyang Liu, Alicia Francis, Nikolay Gabrovski, Eric E. Schadt, Zhen Zhang, Alexey I. Nesvizhskii, Hariharan Easwaran, Huan Chen, Tao Liu, Elizabeth R. Duffy, Liwei Cao, Joshua M. Wang, Michael H.A. Roehrl, Antonio Colaprico, Ana I. Robles, Emily S. Boja, Rita Jui-Hsien Lu, Rodrigo Vargas Eguez, Yize Li, Jennifer M. Koziak, Wenke Liu, Weiming Yang, Arvind Singh Mer, Dana R. Valley, Sailaja Mareedu, Song Cao, Scott D. Jewell, William Bocik, Shilpi Singh, Yongchao Dou, Matthew A. Wyczalkowski, David Fenyö, Galen Hostetter, Liqun Qi, Wenyi Wang, Yvonne Shutack, Shirley Tsang, Karen A. Ketchum, Charles A. Goldthwaite, Katherine A. Hoadley, Richard D. Smith, Karsten Krug, Yuxing Liao, Nadezhda V. Terekhanova, Henry Rodriguez, Barbara Hindenach, Matthew J. Ellis, Yingwei Hu, Pei Wang, Daniel C. Rohrer, Sara R. Savage, Grace Zhao, Ludmila Danilova, Yige Wu, Parham Minoo, Jennifer M. Eschbacher, Nathan Edwards, T. Mamie Lih, Simina M. Boca, George D. Wilson, Alexey Shabunin, Bing Zhang, Michael A. Gillette, Brian J. Druker, David J. Clark, Jianbo Pan, Katarzyna Kusnierz, David Chesla, Ronald Matteotti, Corbin D. Jones, Michael J. Birrer, Lori J. Sokoll, Qing Kay Li, Mehdi Mesri, Peter B. McGarvey, Chet Birger, Barbara Pruetz, Daniel W. Chan, Bo Wen, Nicollette Maunganidze, and Jasmine Huang
Subjects: Adult, Male, Pancreatic ductal adenocarcinoma, Proteome, Gene Dosage, Biology, Adenocarcinoma, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Article, Epigenesis, Genetic, Substrate Specificity, Cohort Studies, medicine, Humans, Molecular Targeted Therapy, Phosphorylation, Aged, Glycoproteins, Proteogenomics, Aged, 80 and over, MicroRNA sequencing, Genome, Human, RNA, Endothelial Cells, Methylation, Middle Aged, Phosphoproteins, Prognosis, Pancreatic Neoplasms, Phenotype, Cancer research, Female, KRAS, Signal transduction, Carcinogenesis, Transcriptome, Glycolysis, Protein Kinases, Algorithms, Carcinoma, Pancreatic Ductal
Abstract: Summary Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.
Published: 2021

2. Small Nucleolar RNA Score: An Assay to Detect Formalin-Overfixed Tissue

Author: Fay Betsou, Pauline Lambert, Dana R. Valley, Daniel C. Rohrer, Olga Kofanova, Johanna Trouet, Alex Blanski, Wim Ammerlaan, Scott D. Jewell, Sonia Frasquilho, Michael C. Sachs, Ping Guan, Latarsha J. Carithers, Helen M. Moore, and Laurent Antunes
Subjects: Quality Control, 0301 basic medicine, Tissue Fixation, Biospecimen, Medicine (miscellaneous), Tissue Banks, Computational biology, Biology, Kidney, General Biochemistry, Genetics and Molecular Biology, Fixatives, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Formaldehyde, microRNA, Humans, RNA, Small Nucleolar, formalin fixation, Small nucleolar RNA, Oligonucleotide Array Sequence Analysis, miRNA, Fixation (histology), Ovarian Neoplasms, Paraffin Embedding, RNA, tissue, Original Articles, Cell Biology, General Medicine, biobank, MicroRNAs, 030104 developmental biology, chemistry, Expression data, 030220 oncology & carcinogenesis, Female, DNA, Small nuclear RNA
Abstract: Although there are millions of formalin-fixed paraffin-embedded (FFPE) tissue blocks potentially available for scientific research, many are of questionable quality, partly due to unknown fixation conditions. We analyzed FFPE tissue biospecimens as part of the NCI Biospecimen Preanalytical Variables (BPV) program to identify microRNA (miRNA) markers for fixation time. miRNA was extracted from kidney and ovary tumor FFPE blocks (19 patients, cold ischemia ≤2 hours) with 6, 12, 24, and 72 hours fixation times, then analyzed using the WaferGen SmartChip platform (miRNA chip with 1036 miRNA targets). For fixation time, principal component analysis of miRNA chip expression data separated 72 hours fixed samples from 6 to 24 hours fixed samples. A set of small nuclear RNA (snRNA) targets was identified that best determines fixation time and was validated using a second independent cohort of seven different tissue types. A customized assay was then developed, based on a set of 24 miRNA and snRNA targets, and a simple “snoRNA score” defined. This score detects FFPE tissue samples with fixation for 72 hours or more, with 79% sensitivity and 80% specificity. It can therefore be used to assess the fitness-for-purpose of FFPE samples for DNA or RNA-based research or clinical assays, which are known to be of limited robustness to formalin overfixation.
Published: 2018

3. Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry

Author: Helen Moore, Galen Hostetter, Kelly B. Engel, Nancy Roche, Scott D. Jewell, Dana R. Valley, Ping Guan, Aditi Bagchi, Kristin Feenstra, Emily Wolfrum, Daniel C. Rohrer, and Zachary Madaj
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Histology, Biospecimen, Tissue Fixation, 03 medical and health sciences, 0302 clinical medicine, Formaldehyde, Survivin, medicine, Biomarkers, Tumor, Humans, Paraffin Embedding, biology, business.industry, CD44, Cancer, Articles, medicine.disease, Immunohistochemistry, Kidney Neoplasms, Staining, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Cancer biomarkers, Anatomy, PAX8, business
Abstract: Analysis of formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemistry (IHC) is commonplace in clinical and research laboratories. However, reports suggest that IHC results can be compromised by biospecimen preanalytical factors. The National Cancer Institute’s Biospecimen Preanalytical Variables Program conducted a systematic study to examine the potential effects of delay to fixation (DTF) and time in fixative (TIF) on IHC using 24 cancer biomarkers. Differences in IHC staining, relative to controls with a DTF of 1 hr, were observed in FFPE kidney tumor specimens after a DTF of ≥2 hr. Reductions in H-score and/or staining intensity were observed for c-MET, p53, PAX2, PAX8, pAKT, and survivin, whereas increases were observed for RCC1, EGFR, and CD10. Prolonged TIF of 72 hr resulted in significantly reduced H-scores of CD44 and c-Met in kidney tumor specimens, compared with controls with 12-hr TIF. An elevated probability of altered staining intensity due to DTF was observed for nine antigens, whereas for prolonged TIF an elevated probability was observed for one antigen. Results reported here and elsewhere across tumor types and antigens support limiting DTF to ≤1 hr when possible and fixing tissues in formalin for 12–24 hr to avoid confounding effects of these preanalytical factors on IHC.
Published: 2021

4. Proteogenomic and metabolomic characterization of human glioblastoma

Author: Cristina E. Tognon, Larisa Polonskaya, Tara Skelly, Shuang Cai, Francesmary Modugno, Larissa Rossell, Nancy Roche, Chen Huang, Jessika Baral, Fulvio D'Angelo, Wen-Wei Liang, Chia-Feng Tsai, Sneha P. Couvillion, Karin D. Rodland, Jun Zhu, Liang-Bo Wang, Paul D. Piehowski, Antonio Colaprico, Anupriya Agarwal, Matthew A. Wyczalkowski, Umut Ozbek, Francesca Petralia, Alexis Demopoulos, William W. Maggio, Lin Chen, Katherine A. Hoadley, Richard D. Smith, Sandra Cottingham, John McGee, Marcin J. Domagalski, Houxiang Zhu, Emek Demir, Rebecca I. Montgomery, Jamie Moon, Rashna Madan, George D. Wilson, Luciano Garofano, Ewa P. Malc, Chelsea J. Newton, Steven A. Carr, Chandan Kumar-Sinha, Donghui Tan, Christopher R. Kinsinger, Oxana Paklina, Weiqing Wan, Stephanie De Young, Sandra Cerda, Shankha Satpathy, Wojciech Kaspera, Linda Hannick, Gad Getz, Runyu Hong, Shuangjia Lu, Ziad Hanhan, Daniel C. Rohrer, Annette Marrero-Oliveras, Wojciech Szopa, Yuxing Liao, Amanda G. Paulovich, Jiayi Ji, Denis A. Golbin, Tara Hiltke, Weiva Sieh, Piotr A. Mieczkowski, Matthew E. Monroe, Gilbert S. Omenn, Jill S. Barnholtz-Sloan, Azra Krek, Bing Zhang, Brittany Henderson, Peter B. McGarvey, Ratna R. Thangudu, Maciej Wiznerowicz, Saravana M. Dhanasekaran, Alex Webster, Kai Li, Karna Robinson, Nan Ji, Karl K. Weitz, Simina M. Boca, Xiaoyu Song, Anna Calinawan, Adam C. Resnick, Brian J. Druker, Dana R. Valley, David J. Clark, Tao Liu, Eric J. Jaehnig, Alicia Francis, Michele Ceccarelli, Rui Zhao, Dmitry Rykunov, Boris Reva, Elizabeth R. Duffy, Antonio Iavarone, Dave Tabor, Joshua F. McMichael, Daniel Cui Zhou, Maureen Dyer, Kimberly Elburn, Scott D. Jewell, Negin Vatanian, Shirley Tsang, Seungyeul Yoo, Alexander R. Pico, Grace Zhao, Kent J. Bloodsworth, Chet Birger, Jena Lilly, Eunkyung An, Jeffrey R. Whiteaker, Albert H. Kim, Yige Wu, Karen A. Ketchum, Felipe D. Leprevost, Alcida Karz, Uma Borate, Nathan Edwards, Uma Velvulou, Melissa Borucki, Vasileios Stathias, Sanford P. Markey, Corbin D. Jones, Ronald J. Moore, MacIntosh Cornwell, Karsten Krug, Michael J. Birrer, James Suh, Tomasz Czernicki, Jason E. McDermott, Emily S. Boja, Pei Wang, Nina Martinez, Wenke Liu, Yan Shi, Lili Blumenberg, Emily Kawaler, Jeffrey W. Tyner, Feng Chen, Jakub Stawicki, Ki Sung Um, Arul M. Chinnaiyan, Robert Zelt, Jacob J. Day, Zhen Zhang, Caleb M. Lindgren, Li Ding, Nikolay Gabrovski, Hongwei Liu, Jonathan T. Lei, Alla Karpova, Ramani B. Kothadia, Sailaja Mareedu, Mitual Amin, Hannah Boekweg, Jennifer E. Kyle, Sara R. Savage, Brian R. Rood, Yuriy Zakhartsev, Matthew L. Anderson, Alyssa Charamut, Wagma Caravan, Shakti Ramkissoon, Junmei Wang, Song Cao, Samuel H. Payne, Rosalie K. Chu, Rajiv Dhir, David W. Andrews, Galen Hostetter, Liqun Qi, Zhiao Shi, Milan G. Chheda, Robert Edwards, Hui Zhang, Weiping Ma, Jennifer M. Eschbacher, Stacey Gabriel, Jan Lubinski, Lijun Yao, Erika M. Zink, Kelly L. Stratton, William Bocik, Mathangi Thiagarajan, Shilpi Singh, Michael A. Gillette, Lisa M. Bramer, Thomas L. Bauer, Michael Vernon, Henry Rodriguez, Dimitris G. Placantonakis, Eric E. Schadt, Alexey I. Nesvizhskii, Vladislav A. Petyuk, Ana I. Robles, Yvonne Shutack, Anna Malovannaya, Stephen E. Stein, Xi Chen, Lyndon Kim, Yize Li, Shannon Richey, Stephan C. Schürer, Barbara Hindenach, Matthew J. Ellis, Yongchao Dou, David Fenyö, Amy M. Perou, Olga Potapova, Shrabanti Chowdhury, Andrew K. Godwin, Marcin Cieślik, Michael C. Wendl, Marina A. Gritsenko, Pietro Pugliese, Elie Traer, Simona Migliozzi, D. R. Mani, Houston Culpepper, Gregory J. Riggins, Xiaolu Yang, Mehdi Mesri, David Chesla, Lindsey K. Olsen, Lori J. Sokoll, Suhas Vasaikar, Liwei Zhang, Meghan C. Burke, Kelly V. Ruggles, Qing Kay Li, Daniel W. Chan, Bo Wen, Nicollette Maunganidze, Darlene Tansil, Joseph H. Rothstein, Barbara Pruetz, Pushpa Hariharan, Wang, L. -B., Karpova, A., Gritsenko, M. A., Kyle, J. E., Cao, S., Li, Y., Rykunov, D., Colaprico, A., Rothstein, J. H., Hong, R., Stathias, V., Cornwell, M., Petralia, F., Wu, Y., Reva, B., Krug, K., Pugliese, P., Kawaler, E., Olsen, L. K., Liang, W. -W., Song, X., Dou, Y., Wendl, M. C., Caravan, W., Liu, W., Cui Zhou, D., Ji, J., Tsai, C. -F., Petyuk, V. A., Moon, J., Ma, W., Chu, R. K., Weitz, K. K., Moore, R. J., Monroe, M. E., Zhao, R., Yang, X., Yoo, S., Krek, A., Demopoulos, A., Zhu, H., Wyczalkowski, M. A., Mcmichael, J. F., Henderson, B. L., Lindgren, C. M., Boekweg, H., Lu, S., Baral, J., Yao, L., Stratton, K. G., Bramer, L. M., Zink, E., Couvillion, S. P., Bloodsworth, K. J., Satpathy, S., Sieh, W., Boca, S. M., Schurer, S., Chen, F., Wiznerowicz, M., Ketchum, K. A., Boja, E. S., Kinsinger, C. R., Robles, A. I., Hiltke, T., Thiagarajan, M., Nesvizhskii, A. I., Zhang, B., Mani, D. R., Ceccarelli, M., Chen, X. S., Cottingham, S. L., Li, Q. K., Kim, A. H., Fenyo, D., Ruggles, K. V., Rodriguez, H., Mesri, M., Payne, S. H., Resnick, A. C., Wang, P., Smith, R. D., Iavarone, A., Chheda, M. G., Barnholtz-Sloan, J. S., Rodland, K. D., Liu, T., Ding, L., Agarwal, A., Amin, M., An, E., Anderson, M. L., Andrews, D. W., Bauer, T., Birger, C., Birrer, M. J., Blumenberg, L., Bocik, W. E., Borate, U., Borucki, M., Burke, M. C., Cai, S., Calinawan, A. P., Carr, S. A., Cerda, S., Chan, D. W., Charamut, A., Chen, L. S., Chesla, D., Chinnaiyan, A. M., Chowdhury, S., Cieslik, M. P., Clark, D. J., Culpepper, H., Czernicki, T., D'Angelo, F., Day, J., De Young, S., Demir, E., Dhanasekaran, S. M., Dhir, R., Domagalski, M. J., Druker, B., Duffy, E., Dyer, M., Edwards, N. J., Edwards, R., Elburn, K., Ellis, M. J., Eschbacher, J., Francis, A., Gabriel, S., Gabrovski, N., Garofano, L., Getz, G., Gillette, M. A., Godwin, A. K., Golbin, D., Hanhan, Z., Hannick, L. I., Hariharan, P., Hindenach, B., Hoadley, K. A., Hostetter, G., Huang, C., Jaehnig, E., Jewell, S. D., Ji, N., Jones, C. D., Karz, A., Kaspera, W., Kim, L., Kothadia, R. B., Kumar-Sinha, C., Lei, J., Leprevost, F. D., Li, K., Liao, Y., Lilly, J., Liu, H., Lubinski, J., Madan, R., Maggio, W., Malc, E., Malovannaya, A., Mareedu, S., Markey, S. P., Marrero-Oliveras, A., Martinez, N., Maunganidze, N., Mcdermott, J. E., Mcgarvey, P. B., Mcgee, J., Mieczkowski, P., Migliozzi, S., Modugno, F., Montgomery, R., Newton, C. J., Omenn, G. S., Ozbek, U., Paklina, O. V., Paulovich, A. G., Perou, A. M., Pico, A. R., Piehowski, P. D., Placantonakis, D. G., Polonskaya, L., Potapova, O., Pruetz, B., Qi, L., Ramkissoon, S., Resnick, A., Richey, S., Riggins, G., Robinson, K., Roche, N., Rohrer, D. C., Rood, B. R., Rossell, L., Savage, S. R., Schadt, E. E., Shi, Y., Shi, Z., Shutack, Y., Singh, S., Skelly, T., Sokoll, L. J., Stawicki, J., Stein, S. E., Suh, J., Szopa, W., Tabor, D., Tan, D., Tansil, D., Thangudu, R. R., Tognon, C., Traer, E., Tsang, S., Tyner, J., Um, K. S., Valley, D. R., Vasaikar, S., Vatanian, N., Velvulou, U., Vernon, M., Wan, W., Wang, J., Webster, A., Wen, B., Whiteaker, J. R., Wilson, G. D., Zakhartsev, Y., Zelt, R., Zhang, H., Zhang, L., Zhang, Z., Zhao, G., and Zhu, J.
Subjects: Proteomics, 0301 basic medicine, Cancer Research, CPTAC, Histone H2B acetylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Computational biology, Biology, Article, 03 medical and health sciences, lipidome, 0302 clinical medicine, Metabolomics, proteogenomic, Humans, Phosphorylation, EP300, proteomic, Proteogenomics, acetylome, single nuclei RNA-seq, Brain Neoplasms, Phospholipase C gamma, glioblastoma, Computational Biology, Lipidome, 030104 developmental biology, Histone, Oncology, Acetylation, 030220 oncology & carcinogenesis, Mutation, biology.protein, metabolome, signaling
Abstract: Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment. Wang et al. perform integrated proteogenomic analysis of adult glioblastoma (GBM), including metabolomics, lipidomics, and single nuclei RNA-Seq, revealing insights into the immune landscape of GBM, cell-specific nature of EMT signatures, histone acetylation in classical GBM, and the existence of signaling hubs which could provide therapeutic vulnerabilities.
Published: 2021

5. A proteogenomic portrait of lung squamous cell carcinoma

Author: Shuang Cai, Elizabeth R. Duffy, Felipe da Veiga Leprevost, D. R. Mani, Antonio Colaprico, Jiayi Ji, Mehdi Mesri, Alicia Francis, Peter B. McGarvey, Myvizhi Esai Selvan, Corbin D. Jones, Michael J. Birrer, Robert J. Welsh, Lori Bernard, Shankha Satpathy, Li Ding, Sara R. Savage, Eugene S. Fedorov, Fernanda Martins Rodrigues, Marcin J. Domagalski, Jennifer M. Eschbacher, Shayan C. Avanessian, Boris Reva, Harsh Batra, Suhas Vasaikar, Nathan Edwards, Michael A. Gillette, Chet Birger, Scott D. Jewell, Kei Suzuki, William Bocik, Shilpi Singh, Meenakshi Anurag, Karen E. Christianson, Namrata D. Udeshi, Vasileios Stathias, Warren G. Tourtellotte, Karl R. Clauser, Shutack, Andrii Karnuta, Dana R. Valley, Kelly V. Ruggles, Qing Kay Li, Amanda G. Paulovich, MacIntosh Cornwell, Shankara Anand, Bartosz Kubisa, Pierre M. Jean Beltran, James Suh, Gilbert S. Omenn, Azra Krek, Wohaib Hasan, Yongchao Dou, David Fenyö, Henry Rodriguez, Samuel H. Payne, Małgorzata Wojtyś, Daniel W. Chan, Bo Wen, Nicollette Maunganidze, Özgün Babur, Renganayaki Pandurengan, Karen A. Ketchum, Nikolay Gabrovski, Pankaj Vats, Saravana M. Dhanasekaran, Richard D. Smith, Gad Getz, Sailaja Mareedu, Yuxing Liao, Mikhail Krotevich, Hui Zhang, Eric J. Jaehnig, Charles A. Goldthwaite, Alexey I. Nesvizhskii, Katherine A. Hoadley, Alexander A. Green, Francesca Petralia, Chandan Kumar-Sinha, Karsten Krug, Eunkyung An, Elena V. Ponomareva, Ximing Tang, Nancy Roche, Daniel C. Rohrer, David I. Heiman, Arul M. Chinnaiyan, Pamela Grady, Rebecca I. Montgomery, Galen Hostetter, Liqun Qi, Stephan C. Schürer, George D. Wilson, Pushpa Hariharan, Zhen Zhang, Yvonne, David Chesla, Chia-Kuei Mo, Maria Gabriela Raso, Negin Vatanian, Paul K. Paik, Fei Ding, Thomas L. Bauer, Barbara Hindenach, Matthew J. Ellis, Chen Huang, Karin D. Rodland, Oluwole Fadare, Ramaswamy Govindan, Eric E. Schadt, Sandra Cottingham, Barbara Pruetz, Sendurai A. Mani, Shirley Tsang, Carissa Huynh, Weiping Ma, Jennifer E. Maas, Tobias Schraink, Stacey Gabriel, Bing Zhang, Tara Hiltke, Rama Soundararajan, Tatiana Omelchenko, Brian J. Druker, Matthew A. Wyczalkowski, Neil R. Mucci, Ziad Hanhan, Donna E. Hansel, Yifat Geffen, Mathangi Thiagarajan, Xiaojun Jing, Pei Wang, Alfredo Molinolo, Tanmayi Vashist, Ratna R. Thangudu, Maciej Wiznerowicz, Edwin R. Parra, Tanvi H. Visal, Maureen Dyer, Melissa Borucki, Ki Sung Um, Jonathan T. Lei, Marcin Cieslik, Christopher R. Kinsinger, M. Harry Kane, Houxiang Zhu, Chelsea J. Newton, Steven A. Carr, Tao Liu, Wenke Liu, Volodymyr Sovenko, Olga Potapova, Eric J. Burks, Song Cao, Ana I. Robles, Yuping Zhang, Yize Li, Midie Xu, Erik J. Bergstrom, Zeynep H. Gümüş, Kai Li, and Xiaoyu Song
Subjects: Adult, Male, Epithelial-Mesenchymal Transition, Lung Neoplasms, Biology, Proteomics, Receptor Tyrosine Kinase-like Orphan Receptors, General Biochemistry, Genetics and Molecular Biology, Article, SOX2, CDKN2A, Survivin, medicine, Cluster Analysis, Humans, Receptors, Platelet-Derived Growth Factor, Phosphorylation, Lung cancer, Aged, Proteogenomics, Aged, 80 and over, EZH2, Ubiquitination, Cyclin-Dependent Kinase 4, Acetylation, Cyclin-Dependent Kinase 6, Middle Aged, medicine.disease, Chromatin, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Mutation, Cancer research, Carcinoma, Squamous Cell, Female, Protein Binding, Signal Transduction
Abstract: Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.
Published: 2020

6. A vast resource of allelic expression data spanning human tissues

Author: Nancy J. Cox, Sayantan Das, Abhi Rao, Pejman Mohammadi, Alan Kwong, Brandon L. Pierce, Yanyu Liang, Yuxin Zou, Anna M. Smith, Matthew Stephens, Chiara Sabatti, Yuan He, Kasper D. Hansen, Lei Hou, Meritxell Oliva, W. James Kent, Stacey Gabriel, Andrew R. Hame, Tanya Krubit, Gary Walters, Lori E. Brigham, Gao Wang, Kevin S. Smith, Michael J. Gloudemans, Barbara E. Engelhardt, Yongjin Park, Nicole A. Teran, David A. Davis, Thomas Juettemann, Kimberley Ramsey, Fred A. Wright, Lin Chen, Valentin Wucher, Benjamin J. Strober, Duyen T. Nguyen, Eleazar Eskin, Kane Hadley, Deborah C. Mash, Michael Snyder, Sarah Kim-Hellmuth, Laura A. Siminoff, Maghboeba Mosavel, Shin Lin, Richard Hasz, Daniel C. Rohrer, Latarsha J. Carithers, Kevin Myer, Rajinder Kaul, Andrew D. Skol, Bryan Gillard, Dana R. Valley, Philip A. Branton, Stephane E. Castel, Robert E. Handsaker, Debra Bradbury, Meng Wang, Mary Barcus, Xiaoquan Wen, Hua Tang, Daniel J. Cotter, Lihua Jiang, Jason Bridge, Ashis Saha, Gen Li, Susan E. Koester, Qin Li, Mark H. Johnson, Barbara E. Stranger, Jimmie B. Vaught, Hae Kyung Im, Paul Flicek, Marcus Hunter, François Aguet, Elise D. Flynn, Sandra Linder, Nancy Roche, Daniel R. Zerbino, Xiao Li, Barbara A. Foster, Stephen B. Montgomery, Daniel Nachun, Serghei Mangul, Emmanouil T. Dermitzakis, Brian Jo, Simona Volpi, Farzana Jasmine, Scott D. Jewell, Jonah Einson, Tuuli Lappalainen, Farhad Hormozdiari, John M. Rouhana, Ana Viñuela, Daniel G. MacArthur, William F. Leinweber, Gad Getz, Peter Hickey, Eric R. Gamazon, Brunilda Balliu, Jennifer A. Doherty, Christopher D. Brown, Roderic Guigó, Gene Kopen, Rodrigo Bonazzola, Pedro G. Ferreira, Andrew P. Feinberg, Shankara Anand, Helen M. Moore, Paul J. Hoffman, Heather M. Gardiner, Ping Guan, Ferran Reverter, Jin Billy Li, Tiffany Eulalio, Joseph Wheeler, Alvaro N. Barbeira, Jared L. Nedzel, Seva Kashin, Laure Fresard, Lindsay F. Rizzardi, Abhiram Rao, Muhammad G. Kibriya, David Tabor, Leslie H. Sobin, A. Roger Little, Stephen J. Trevanion, Nicole M. Ferraro, Kate R. Rosenbloom, John A. Stamatoyannopoulos, Liqun Qi, Princy Parsana, Ayellet V. Segrè, Dan Sheppard, Nathan S. Abell, Kathryn Demanelis, Manolis Kellis, Silva Kasela, Xin Li, Conner C. Powell, YoSon Park, Michael Washington, Magali Ruffier, Saboor Shad, Christopher Johns, Jeffrey A. Thomas, Andrew Brown, Alisa McDonald, Karna Robinson, Esti Yeger-Lotem, Manuel Muñoz-Aguirre, Kieron Taylor, Marta Melé, Diego Garrido-Martín, Brian Roe, Michael T. Moser, Andrew B. Nobel, Alexis Battle, Maximilian Haeussler, Concepcion R. Nierras, Ellen Karasik, Sam Meier, Anita H. Undale, Ellen Todres, Aaron Graubert, Joshua M. Akey, Jeffrey McLean, Donald F. Conrad, Olivia M. De Goede, Katherine H. Huang, Laura Barker, Kristin G. Ardlie, and Christopher Lee
Subjects: animal structures, Future studies, lcsh:QH426-470, Short Report, Gene Expression, Genomics, Computational biology, Biology, eQTL, Polymorphism, Single Nucleotide, ASE, Regulatory variation, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), Humans, SNP, Allele, lcsh:QH301-705.5, Alleles, Allele specific, 030304 developmental biology, 0303 health sciences, Allelic expression, Genome, Human, Sequence Analysis, RNA, Haplotype, Functional genomics, Human genetics, lcsh:Genetics, Haplotypes, lcsh:Biology (General), Expression data, Expression quantitative trait loci, GTEx, 030217 neurology & neurosurgery
Abstract: Allele expression (AE) analysis robustly measures cis-regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from the GTEx v8 release, containing 15,253 samples spanning 54 human tissues for a total of 431 million measurements of AE at the SNP level and 153 million measurements at the haplotype level. In addition, we develop an extension of our tool phASER that allows effect sizes of cis-regulatory variants to be estimated using haplotype-level AE data. This AE resource is the largest to date, and we are able to make haplotype-level data publicly available. We anticipate that the availability of this resource will enable future studies of regulatory variation across human tissues.
Published: 2020

7. Great Lakes Biorepository Research Network's Annual Biobanking Symposium: A Focus on Precision Medicine

Author: Joseph D. Paulauskis, Renée C Frey, Timothy J. Geddes, Jonathan J Keats, Thomas E. Carey, Daniel C. Rohrer, David Chesla, George S. Wilson, Jan Akervall, Scott D. Jewell, Tom Tomlinson, Dana R. Valley, Barbara L. Pruetz, Allan Loup, and Victoria M. Blanc
Subjects: Focus (computing), Brief Report, MEDLINE, Medicine (miscellaneous), Biological Specimen Banks, Cell Biology, General Medicine, Biology, Congresses as Topic, Precision medicine, Biobank, Data science, General Biochemistry, Genetics and Molecular Biology, Specimen Handling, Biorepository, Humans, Intersectoral Collaboration, Great Lakes Region, Precision Medicine
Published: 2019

8. Cold Ischemia Score: An mRNA Assay for the Detection of Extended Cold Ischemia in Formalin-Fixed, Paraffin-Embedded Tissue

Author: Dana R. Valley, Latarsha J. Carithers, Fay Betsou, Conny Mathay, Kathleen Mommaerts, William Mathieson, Alexander Blanski, Daniel C. Rohrer, Johanna Trouet, Helen M. Moore, Scott D. Jewell, and Ping Guan
Subjects: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Histology, Biospecimen, Time Factors, Tissue Fixation, Formalin fixed paraffin embedded, 03 medical and health sciences, Fixatives, 0302 clinical medicine, Formaldehyde, medicine, Humans, RNA, Messenger, Cold ischemia, Stable gene, Ovarian Neoplasms, Messenger RNA, Kidney, Cold ischemic time, Paraffin Embedding, business.industry, Reverse Transcriptase Polymerase Chain Reaction, Cold Ischemia, Cancer, Articles, medicine.disease, Kidney Neoplasms, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Anatomy, business, Transcriptome
Abstract: Although there are thousands of formalin-fixed paraffin-embedded (FFPE) tissue blocks potentially available for scientific research, many are of questionable quality, partly due to unknown preanalytical variables. We analyzed FFPE tissue biospecimens as part of the National Cancer Institute (NCI) Biospecimen Preanalytical Variables program to identify mRNA markers denoting cold ischemic time. The mRNA was extracted from colon, kidney, and ovary cancer FFPE blocks (40 patients, 10–12 hr fixation time) with 1, 2, 3, and 12 hr cold ischemic times, then analyzed using qRT-PCR for 23 genes selected following a literature search. No genes tested could determine short ischemic times (1–3 hr). However, a combination of three unstable genes normalized to a more stable gene could generate a “Cold Ischemia Score” that could distinguish 1 to 3 hr cold ischemia from 12 hr cold ischemia with 62% sensitivity and 84% specificity.
Published: 2018

9. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

Author: Olivia M. de Goede, Daniel C. Nachun, Nicole M. Ferraro, Michael J. Gloudemans, Abhiram S. Rao, Craig Smail, Tiffany Y. Eulalio, François Aguet, Bernard Ng, Jishu Xu, Alvaro N. Barbeira, Stephane E. Castel, Sarah Kim-Hellmuth, YoSon Park, Alexandra J. Scott, Benjamin J. Strober, Christopher D. Brown, Xiaoquan Wen, Ira M. Hall, Alexis Battle, Tuuli Lappalainen, Hae Kyung Im, Kristin G. Ardlie, Sara Mostafavi, Thomas Quertermous, Karla Kirkegaard, Stephen B. Montgomery, Shankara Anand, Stacey Gabriel, Gad A. Getz, Aaron Graubert, Kane Hadley, Robert E. Handsaker, Katherine H. Huang, Xiao Li, Daniel G. MacArthur, Samuel R. Meier, Jared L. Nedzel, Duyen T. Nguyen, Ayellet V. Segrè, Ellen Todres, Brunilda Balliu, Rodrigo Bonazzola, Andrew Brown, Donald F. Conrad, Daniel J. Cotter, Nancy Cox, Sayantan Das, Emmanouil T. Dermitzakis, Jonah Einson, Barbara E. Engelhardt, Eleazar Eskin, Elise D. Flynn, Laure Fresard, Eric R. Gamazon, Diego Garrido-Martín, Nicole R. Gay, Roderic Guigó, Andrew R. Hamel, Yuan He, Paul J. Hoffman, Farhad Hormozdiari, Lei Hou, Brian Jo, Silva Kasela, Seva Kashin, Manolis Kellis, Alan Kwong, Xin Li, Yanyu Liang, Serghei Mangul, Pejman Mohammadi, Manuel Muñoz-Aguirre, Andrew B. Nobel, Meritxell Oliva, Yongjin Park, Princy Parsana, Ferran Reverter, John M. Rouhana, Chiara Sabatti, Ashis Saha, Matthew Stephens, Barbara E. Stranger, Nicole A. Teran, Ana Viñuela, Gao Wang, Fred Wright, Valentin Wucher, Yuxin Zou, Pedro G. Ferreira, Gen Li, Marta Melé, Esti Yeger-Lotem, Debra Bradbury, Tanya Krubit, Jeffrey A. McLean, Liqun Qi, Karna Robinson, Nancy V. Roche, Anna M. Smith, David E. Tabor, Anita Undale, Jason Bridge, Lori E. Brigham, Barbara A. Foster, Bryan M. Gillard, Richard Hasz, Marcus Hunter, Christopher Johns, Mark Johnson, Ellen Karasik, Gene Kopen, William F. Leinweber, Alisa McDonald, Michael T. Moser, Kevin Myer, Kimberley D. Ramsey, Brian Roe, Saboor Shad, Jeffrey A. Thomas, Gary Walters, Michael Washington, Joseph Wheeler, Scott D. Jewell, Daniel C. Rohrer, Dana R. Valley, David A. Davis, Deborah C. Mash, Mary E. Barcus, Philip A. Branton, Leslie Sobin, Laura K. Barker, Heather M. Gardiner, Maghboeba Mosavel, Laura A. Siminoff, Paul Flicek, Maximilian Haeussler, Thomas Juettemann, W. James Kent, Christopher M. Lee, Conner C. Powell, Kate R. Rosenbloom, Magali Ruffier, Dan Sheppard, Kieron Taylor, Stephen J. Trevanion, Daniel R. Zerbino, Nathan S. Abell, Joshua Akey, Lin Chen, Kathryn Demanelis, Jennifer A. Doherty, Andrew P. Feinberg, Kasper D. Hansen, Peter F. Hickey, Farzana Jasmine, Lihua Jiang, Rajinder Kaul, Muhammad G. Kibriya, Jin Billy Li, Qin Li, Shin Lin, Sandra E. Linder, Brandon L. Pierce, Lindsay F. Rizzardi, Andrew D. Skol, Kevin S. Smith, Michael Snyder, John Stamatoyannopoulos, Hua Tang, Meng Wang, Latarsha J. Carithers, Ping Guan, Susan E. Koester, A. Roger Little, Helen M. Moore, Concepcion R. Nierras, Abhi K. Rao, Jimmie B. Vaught, and Simona Volpi
Subjects: Multifactorial Inheritance, Population, Quantitative Trait Loci, Coronary Artery Disease, Disease, Computational biology, Quantitative trait locus, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Humans, education, Gene, 030304 developmental biology, 0303 health sciences, education.field_of_study, Gene Expression Profiling, Genetic Variation, Inflammatory Bowel Diseases, Long non-coding RNA, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Organ Specificity, Expression quantitative trait loci, Trait, RNA, Long Noncoding, 030217 neurology & neurosurgery
Abstract: Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.
Published: 2021

10. Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

Author: Tara Skelly, Wen Jiang, Zhen Zhang, Anupriya Agarwal, Amy M. Perou, Olga Potapova, Christopher R. Kinsinger, Matthew A. Wyczalkowski, David J. Clark, Shuang Cai, Felipe da Veiga Leprevost, Linda Hannick, Chen Huang, Paul D. Piehowski, John McGee, Marcin J. Domagalski, Dmitris Placantonakis, Jianbo Pan, Dana R. Valley, Zhiao Shi, Hui Yin Chang, Karen A. Ketchum, Charles A. Goldthwaite, Małgorzata Wierzbicka, Karsten Krug, Yvonne Shutack, Sara R. Savage, Matthew L. Anderson, Alyssa Charamut, Chandan Kumar-Sinha, Sanford P. Markey, Ratna R. Thangudu, Weiping Ma, Oliver F. Bathe, Antonio Colaprico, Yuxing Liao, Eric E. Schadt, Tomasz Czernicki, Seungyeul Yoo, Xi Chen, Stacey Gabriel, Karl R. Clauser, Daniel C. Rohrer, Uma Borate, Uma Velvulou, Larisa Polonskaya, M. Harry Kane, Dmitry M. Avtonomov, Boris Reva, Jacob J. Day, Barbara Hindenach, Matthew J. Ellis, Katherine A. Hoadley, Emek Demir, Rebecca I. Montgomery, Ewa P. Malc, Fengchao Yu, Lijun Yao, Maciej Wiznerowicz, Annette Marrero-Oliveras, Wojciech Szopa, Sailaja Mareedu, Galen Hostetter, Liqun Qi, Hui Zhang, Yige Wu, David N. Hayes, Shankha Satpathy, Corbin D. Jones, Michael J. Birrer, Xinpei Yi, Nathan Edwards, Fei Ding, Jiang Qian, Ning Qu, Alicia Francis, Daniel Cui Zhou, Jakub Stawicki, Bing Zhang, Rodrigo Vargas Eguez, Tao Liu, Dave Tabor, Maureen Dyer, Brian J. Druker, Gilbert S. Omenn, Azra Krek, Meenakshi Anurag, Melissa Borucki, Mathangi Thiagarajan, Shirley Tsang, Shakti Ramkissoon, Alexey I. Nesvizhskii, Li Ding, Lyubomir Valkov Vasilev, Yifat Geffen, James Suh, Tatiana S. Ermakova, Kakhaber Zaalishvili, Adel K. El-Naggar, Ki Sung Um, Ana I. Robles, Wen-Wei Liang, Richard D. Smith, Pei Wang, Emily S. Boja, Anna Calinawan, Yingwei Hu, Jiayi Ji, Renata Ferrarotto, Hongwei Liu, Jonathan T. Lei, Ramani B. Kothadia, Yize Li, Chelsea J. Newton, Anna Malovannaya, Steven A. Carr, Sandra Cerda, Yuriy Zakhartsev, Stephanie De Young, Eric J. Jaehnig, Peter B. McGarvey, Yan Shi, David I. Heiman, Joseph C. Dort, Karin D. Rodland, Lili Blumenberg, Michael A. Gillette, Piotr A. Mieczkowski, Pankaj Vats, Chet Birger, Yongchao Dou, David Fenyö, Saravana M. Dhanasekaran, Pushpa Hariharan, Eunkyung An, Jeffrey R. Whiteaker, George Miles, Jan Lubinski, Shayan C. Avanessian, Samuel H. Payne, Amanda G. Paulovich, Dmitry Rykunov, Lyudmila Petrenko, Martin Hyrcza, Guo Ci Teo, Alissa M. Weaver, D. R. Mani, Houston Culpepper, Meghan C. Burke, Daniel W. Chan, Bo Wen, Nicollette Maunganidze, Elie Traer, Darlene Tansil, Simona Migliozzi, Luciano Garofano, Qing Kay Li, Donghui Tan, Lori J. Sokoll, Mehdi Mesri, Karna Robinson, Fulvio D'Angelo, Kimberly Elburn, Alexander R. Pico, Umut Ozbek, Michael Schnaubelt, Gad Getz, Francesca Petralia, Andrew G. Sikora, Kai Li, Elena V. Ponomareva, Arul M. Chinnaiyan, Robert Zelt, Jun Zhu, Midie Xu, Dimitar Dimitrov Pazardzhikliev, Negin Vatanian, Grace Zhao, Thomas F. Westbrook, Kyung-Cho Cho, Yuefan Wang, Jason E. McDermott, Jeffrey W. Tyner, William Bocik, Shilpi Singh, Stephen E. Stein, Nancy Roche, Alicia Karz, Shannon Richey, Tara Hiltke, Michael Vernon, Lijun Chen, Henry Rodriguez, Xiaoyu Song, Elizabeth R. Duffy, Lin S. Chen, Liwei Cao, Shrabanti Chowdhury, Marcin Cieślik, Michael C. Wendl, Scott D. Jewell, and Cristina E. Tognon
Subjects: Adult, Male, Proteomics, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Cell, Biology, Article, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Cyclin-dependent kinase, medicine, Humans, Aged, Proteogenomics, Aged, 80 and over, Squamous Cell Carcinoma of Head and Neck, Papillomavirus Infections, Phosphoproteomics, Immunotherapy, Middle Aged, medicine.disease, Head and neck squamous-cell carcinoma, Immune checkpoint, ErbB Receptors, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female
Abstract: We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.
Published: 2021

11. A Quantitative Proteome Map of the Human Body

Author: Lihua Jiang, Meng Wang, Shin Lin, Ruiqi Jian, Xiao Li, Joanne Chan, Guanlan Dong, Huaying Fang, Aaron E. Robinson, Michael P. Snyder, François Aguet, Shankara Anand, Kristin G. Ardlie, Stacey Gabriel, Gad Getz, Aaron Graubert, Kane Hadley, Robert E. Handsaker, Katherine H. Huang, Seva Kashin, Daniel G. MacArthur, Samuel R. Meier, Jared L. Nedzel, Duyen Y. Nguyen, Ayellet V. Segrè, Ellen Todres, Brunilda Balliu, Alvaro N. Barbeira, Alexis Battle, Rodrigo Bonazzola, Andrew Brown, Christopher D. Brown, Stephane E. Castel, Don Conrad, Daniel J. Cotter, Nancy Cox, Sayantan Das, Olivia M. de Goede, Emmanouil T. Dermitzakis, Barbara E. Engelhardt, Eleazar Eskin, Tiffany Y. Eulalio, Nicole M. Ferraro, Elise Flynn, Laure Fresard, Eric R. Gamazon, Diego Garrido-Martín, Nicole R. Gay, Roderic Guigó, Andrew R. Hamel, Yuan He, Paul J. Hoffman, Farhad Hormozdiari, Lei Hou, Hae Kyung Im, Brian Jo, Silva Kasela, Manolis Kellis, Sarah Kim-Hellmuth, Alan Kwong, Tuuli Lappalainen, Xin Li, Yanyu Liang, Serghei Mangul, Pejman Mohammadi, Stephen B. Montgomery, Manuel Muñoz-Aguirre, Daniel C. Nachun, Andrew B. Nobel, Meritxell Oliva, YoSon Park, Yongjin Park, Princy Parsana, Ferran Reverter, John M. Rouhana, Chiara Sabatti, Ashis Saha, Andrew D. Skol, Matthew Stephens, Barbara E. Stranger, Benjamin J. Strober, Nicole A. Teran, Ana Viñuela, Gao Wang, Xiaoquan Wen, Fred Wright, Valentin Wucher, Yuxin Zou, Pedro G. Ferreira, Gen Li, Marta Melé, Esti Yeger-Lotem, Mary E. Barcus, Debra Bradbury, Tanya Krubit, Jeffrey A. McLean, Liqun Qi, Karna Robinson, Nancy V. Roche, Anna M. Smith, Leslie Sobin, David E. Tabor, Anita Undale, Jason Bridge, Lori E. Brigham, Barbara A. Foster, Bryan M. Gillard, Richard Hasz, Marcus Hunter, Christopher Johns, Mark Johnson, Ellen Karasik, Gene Kopen, William F. Leinweber, Alisa McDonald, Michael T. Moser, Kevin Myer, Kimberley D. Ramsey, Brian Roe, Saboor Shad, Jeffrey A. Thomas, Gary Walters, Michael Washington, Joseph Wheeler, Scott D. Jewell, Daniel C. Rohrer, Dana R. Valley, David A. Davis, Deborah C. Mash, Philip A. Branton, Laura K. Barker, Heather M. Gardiner, Maghboeba Mosavel, Laura A. Siminoff, Paul Flicek, Maximilian Haeussler, Thomas Juettemann, W. James Kent, Christopher M. Lee, Conner C. Powell, Kate R. Rosenbloom, Magali Ruffier, Dan Sheppard, Kieron Taylor, Stephen J. Trevanion, Daniel R. Zerbino, Nathan S. Abell, Joshua Akey, Lin Chen, Kathryn Demanelis, Jennifer A. Doherty, Andrew P. Feinberg, Kasper D. Hansen, Peter F. Hickey, Farzana Jasmine, Rajinder Kaul, Muhammad G. Kibriya, Jin Billy Li, Qin Li, Sandra E. Linder, Brandon L. Pierce, Lindsay F. Rizzardi, Kevin S. Smith, John Stamatoyannopoulos, Hua Tang, Latarsha J. Carithers, Ping Guan, Susan E. Koester, A. Roger Little, Helen M. Moore, Concepcion R. Nierras, Abhi K. Rao, Jimmie B. Vaught, and Simona Volpi
Subjects: Proteomics, Cell signaling, Proteome, Quantitative proteomics, Gene Expression, Disease, Computational biology, Biology, ENCODE, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Humans, Secretion, RNA, Messenger, Gene, 030304 developmental biology, 0303 health sciences, Gene Expression Profiling, RNA, Metabolism, Phenotype, Secretory protein, 030217 neurology & neurosurgery
Abstract: Determining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from 12,627 genes across 32 normal human tissue types prepared by the GTEx project. Known and new tissue specific or enriched proteins (5,499) were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode highly tissue specific proteins. Discordance in the sites of RNA expression and protein detection also revealed potential sites of synthesis and action of protein signaling molecules. Overall, these results provide an extraordinary resource, and demonstrate that understanding protein levels can provide insights into metabolism, regulation, secretome, and human diseases.SummaryQuantitative proteome study of 32 human tissues and integrated analysis with transcriptome data revealed that understanding protein levels could provide in-depth knowledge to post transcriptional or translational regulations, human metabolism, secretome, and diseases.
Published: 2020

12. Proteogenomic Characterization of Endometrial Carcinoma

Author: David J. Clark, Jiayi Ji, Beom-Jun Kim, Doug W. Chan, Zhen Zhang, Kim Elburn, Munziba Khan, Katherine Fuh, Katherine A. Hoadley, Jeffrey R. Whiteaker, Peter B. McGarvey, Dana R. Valley, Douglas A. Levine, Sanford P. Markey, Hui Zhang, Tanya Krubit, Christopher R. Kinsinger, Hui Yin Chang, Yuxing Liao, Karen A. Ketchum, Piotr A. Mieczkowski, Pankaj Vats, Matthew E. Monroe, Donghui Tan, Alex Webster, Chet Birger, Kai Li, Ramani Kothadia, Saravana M. Dhanasekaran, Sara R. Savage, Karsten Krug, Marcin Jędryka, Matthew L. Anderson, Alyssa Charamut, Alexander R. Pico, Amanda G. Paulovich, Karna Robinson, Hua Zhou, John McGee, Sean J.I. Beecroft, Amanda E. Oliphant, Annette Marrero-Oliveras, Dmitry Rykunov, Shuang Cai, Francesmary Modugno, Marcin J. Domagalski, Emily Kawaler, Mehdi Mesri, Dmitry M. Avtonomov, Milan G. Chheda, Sue Hilsenbeck, Gilbert S. Omenn, Emek Demir, Rebecca I. Montgomery, Qingsong Gao, Azra Krek, Eric E. Schadt, Li Ding, George D. Wilson, Stephen E. Stein, David Chesla, Gad Getz, Negin Vatanian, Thomas F. Westbrook, Deborah DeLair, David I. Heiman, Karl R. Clauser, Rafal Matkowski, Lori J. Sokoll, Uma Borate, Antonio Colaprico, Jin Chen, Eric J. Jaehnig, Karin D. Rodland, Richard D. Smith, Linda Hannick, Uma Velvulou, Shannon Richey, Andrzej Czekański, Bing Zhang, Arul M. Chinnaiyan, Robert Zelt, Daniel J. Geiszler, Emily L. Hoskins, Ronald J. Moore, Pushpa Hariharan, Suhas Vasaikar, Jason E. McDermott, Yige Wu, Anna Malovannaya, Brian J. Druker, Jeffrey W. Tyner, Yan Shi, Lili Blumenberg, Jamie Moon, Cristina E. Tognon, Chandan Kumar-Sinha, Nathan Edwards, Yifat Geffen, Barbara Hindenach, Matthew J. Ellis, Zhi Li, Michael Schnaubelt, David C. Wheeler, Tara Skelly, Ewa P. Malc, Shrabanti Chowdhury, Andrew K. Godwin, Zhiao Shi, Francesca Petralia, Lin Chen, Scott D. Jewell, Daniel C. Rohrer, Elie Traer, Michael Ittmann, Shankha Satpathy, Marcin Cieslik, Weiping Ma, Daniel Cui Zhou, Maureen Dyer, Boris Reva, Rashna Madan, William Bocik, Stacey Gabriel, Stephanie De Young, Yosef E. Maruvka, Sandra Cottingham, Pamela Grady, D. R. Mani, Houston Culpepper, Meenakshi Anurag, Michael T. Lewis, Anupriya Agarwal, Felipe D. Leprevost, Jonathan C. Jarman, Michael Vernon, Henry Rodriguez, Matthew A. Wyczalkowski, Rui Zhao, Vladislav A. Petyuk, Michelle Chaikin, James Suh, Daniel W. Chan, Bo Wen, Patricia Castro, Alexey I. Nesvizhskii, Chia-Feng Tsai, Grace Zhao, Alicia Francis, Feng Chen, Mathangi Thiagarajan, Pei Wang, Marina A. Gritsenko, Anna Calinawan, David G. Mutch, Melissa Borucki, Xi Steven Chen, Guo Ci Teo, Peter Dottino, Corbin D. Jones, Michael J. Birrer, Ying Wang, Meghan C. Burke, MacIntosh Cornwell, Song Cao, Rosalie K. Chu, Larisa Polonskaya, Samuel H. Payne, Darlene Tansil, Yongchao Dou, David Fenyö, Kelly V. Ruggles, Qing Kay Li, Yuping Zhang, James J. Hsieh, Andy T. Kong, Ana I. Robles, Emily S. Boja, Chelsea J. Newton, Steven A. Carr, Sandra Cerda, Runyu Hong, Jacob J. Day, Sailaja Mareedu, Jan Lubinski, Galen Hostetter, Liqun Qi, Yize Li, Chen Huang, Liang-Bo Wang, Tao Liu, Renee Karabon, Paul D. Piehowski, Samuel L. Pugh, Maciej Wiznerowicz, Ratna R. Thangudu, Wenke Liu, Jayson B. Field, Sonya Carter, Ki Sung Um, Hongwei Liu, Alla Karpova, Yuriy Zakhartsev, Amy M. Perou, Michael S. Noble, Rajiv Dhir, Nancy Roche, Sunantha Sethuraman, Tara Hiltke, Lijun Chen, Xiaoyu Song, Elizabeth R. Duffy, Robert Edwards, Yingwei Hu, John A. Martignetti, Simina M. Boca, Michael A. Gillette, and David W Adams
Subjects: Epithelial-Mesenchymal Transition, Proteome, Druggability, Biology, Proteomics, Genomic Instability, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigens, Neoplasm, medicine, Animals, Humans, Phosphorylation, 030304 developmental biology, Feedback, Physiological, 0303 health sciences, Endometrial cancer, Carcinoma, Wnt signaling pathway, Cancer, Acetylation, medicine.disease, Proteogenomics, Endometrial Neoplasms, Gene Expression Regulation, Neoplastic, MicroRNAs, Serous fluid, Histone, Cancer research, biology.protein, Female, Transcriptome, Protein Processing, Post-Translational, 030217 neurology & neurosurgery, Microsatellite Repeats, Signal Transduction
Abstract: We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.
Published: 2020

13. Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

Author: David J. Clark, Jianbo Pan, Gerald W. Hart, Katherine A. Hoadley, Negin Vatanian, Shuang Cai, Yige Wu, Felipe da Veiga Leprevost, A. Ari Hakimi, Sanford P. Markey, Thomas F. Westbrook, Maciej Wiznerowicz, Nathan Edwards, Alla Y. Karpova, Sohini Sengupta, Marcin Cieslik, Samuel H. Payne, Xi Steven Chen, Guo Ci Teo, Jin Chen, Boris Reva, Corbin D. Jones, Michael J. Birrer, Ying Wang, Kelly V. Ruggles, Doug W. Chan, John McGee, Marcin J. Domagalski, Song Cao, Linda Hannick, Christopher R. Kinsinger, David I. Heiman, Jennifer M. Eschbacher, Munziba Khan, Jason E. McDermott, Dmitry M. Avtonomov, Sue Hilsenbeck, Qing Kay Li, Jiayi Ji, Emek Demir, Rebecca I. Montgomery, Qingsong Gao, Beom-Jun Kim, Xiaoyu Song, Karl R. Clauser, Christian P. Pavlovich, Richard D. Smith, Maureen Dyer, Jeffrey W. Tyner, Amy M. Perou, Yuping Zhang, Dana R. Valley, George D. Wilson, Shiyong Ma, Minghui Ao, Jiang Qian, Umut Ozbek, Melissa Borucki, Zhi Li, Michael Schnaubelt, Chen Huang, Piotr A. Mieczkowski, Francesca Petralia, Abdul Samad Hashimi, Hui Yin Chang, Liang-Bo Wang, Matthew E. Monroe, Peter B. McGarvey, Tao Liu, Karen A. Ketchum, Hui Zhang, Bing Zhang, D. R. Mani, Houston Culpepper, Hua Zhou, Saravana M. Dhanasekaran, Paul D. Piehowski, Zhidong Tu, Brian J. Druker, Ki Sung Um, Zhiao Shi, Uma Borate, Uma Velvulou, Michael Ittmann, Weiping Ma, Steven M. Foltz, Heng Zhu, Stacey Gabriel, Hongwei Liu, Ramani B. Kothadia, Lin Chen, Ewa P. Malc, Marina A. Gritsenko, Jun Zhu, David Chesla, Lori J. Sokoll, Stephen E. Stein, Andrzej Antczak, Matthew L. Anderson, Alyssa Charamut, Pamela Grady, Michael T. Lewis, Shannon Richey, Tanya Krubit, Alexander R. Pico, Kyung-Cho Cho, Daniel C. Rohrer, Francesmary Modugno, Stephanie De Young, Li Ding, Michael Smith, Mathangi Thiagarajan, Alexey I. Nesvizhskii, Shrabanti Chowdhury, Noam D. Beckmann, Kimberly R. Holloway, Ratna R. Thangudu, Sherri R. Davies, Tung-Shing M. Lih, Nicole Tignor, Anna Calinawan, Meghan C. Burke, Karna Robinson, Chet Birger, Shalin Patel, Antonio Colaprico, Sarah Keegan, Daniel J. Geiszler, Scott D. Jewell, William Bocik, Snehal Patil, Pei Wang, MacIntosh Cornwell, Emily Kawaler, Seungyeul Yoo, Jasmine Huang, Vladislav A. Petyuk, Ross Bremner, Donghui Tan, Stefani N. Thomas, Emily S. Boja, Anna Malovannaya, Xi Chen, Wenke Liu, Eric E. Schadt, Shankha Satpathy, Nancy Roche, Rajiv Dhir, Cristina E. Tognon, Michelle Chaikin, Gabriel Bromiński, Daniel C. Zhou, Yifat Geffen, Tara Skelly, Jacob J. Day, Sunantha Sethuraman, Sonya Carter, Zhen Zhang, Selim Kalayci, Michael Vernon, Zeynep H. Gümüş, Kai Li, Barbara Hindenach, Matthew J. Ellis, Meenakshi Anurag, David C. Wheeler, Sailaja Mareedu, Andy T. Kong, Arul M. Chinnaiyan, Robert Zelt, Annette Marrero-Oliveras, Henry Rodriguez, James Suh, Anupriya Agarwal, David Fenyö, Galen Hostetter, Liqun Qi, Matthew A. Wyczalkowski, W. Marston Linehan, Tara Hiltke, Feng Chen, Lijun Chen, Jan Lubinski, Chelsea J. Newton, Steven A. Carr, Tatiana Omelchenko, Gilbert S. Omenn, Karsten Krug, Ana I. Robles, Azra Krek, Runyu Hong, Milan G. Chheda, Yize Li, Yan Shi, Lili Blumenberg, Ruiyang Liu, Karin D. Rodland, Hua Sun, Kim Elburn, Jeffrey R. Whiteaker, Christopher J. Ricketts, Gaddy Getz, Daniel W. Chan, Bo Wen, Robert Edwards, Patricia Castro, Yingwei Hu, Pushpa Hariharan, Simina M. Boca, Darlene Tansil, Phillip M. Pierorazio, Yosef E. Maruvka, Sandra Cottingham, James J. Hsieh, Amanda G. Paulovich, Barbara Pruetz, Michael A. Gillette, Yihao Lu, Dmitry Rykunov, Mehdi Mesri, Marc M. Loriaux, Reyka G Jayasinghe, and Suhas Vasaikar
Subjects: Adult, Male, Cell, Computational biology, Biology, Proteomics, Disease-Free Survival, Oxidative Phosphorylation, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, medicine, Biomarkers, Tumor, Tumor Microenvironment, Humans, Exome, Phosphorylation, Carcinoma, Renal Cell, 030304 developmental biology, Epigenomics, Aged, Proteogenomics, Aged, 80 and over, 0303 health sciences, Tumor microenvironment, Genome, Human, Phosphoproteomics, Middle Aged, medicine.disease, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Clear cell renal cell carcinoma, medicine.anatomical_structure, Female, 030217 neurology & neurosurgery, Signal Transduction
Abstract: SUMMARY To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology., Graphical Abstract, In Brief Comprehensive proteogenomic characterization in 103 treatment-naive clear cell renal cell carcinoma patient samples highlights tumor-specific alterations at the proteomic level that are unrevealed by transcriptomic profiling and proposes a revised subtyping scheme based on integrated omics analysis.
Published: 2020

14. Co-expression networks reveal the tissue-specific regulation of transcription and splicing

Author: Morgan Diegel, Laure Fresard, Lindsay F. Rizzardi, Yuan He, Monkol Lek, Daniel C. Rohrer, Boxiang Liu, Maximilian Haeussler, Heather M. Traino, Concepcion R. Nierras, Joseph Wheeler, Serghei Mangul, Fan Wu, Hualin S. Xi, Andrew D. Skol, Steven Hunter, Yaping Liu, Casandra A. Trowbridge, Brandon L. Pierce, Daniel Bates, Peter Hickey, Susan E. Koester, Bryan Gillard, Eric R. Gamazon, Jennifer A. Doherty, Jared L. Nedzel, Eric Haugen, Lori E. Brigham, Gao Wang, Dana R. Valley, Zachary Zappala, Emmanouil T. Dermitzakis, Seva Kashin, Ira M. Hall, John Vivian, Philip A. Branton, Barbara E. Stranger, Magali Ruffier, Melina Claussnitzer, Nancy Roche, Michael Washington, Halit Ongen, Brian Jo, Rachna Kumar, Jean Monlong, Yi-Hui Zhou, Kristen Lee, Stephane E. Castel, Mark Miklos, Alisa McDonald, Diego Garrido-Martín, Jimmie B. Vaught, Hae Kyung Im, Leslie H. Sobin, John T. Lonsdale, Audra K. Johnson, Rui Zhang, Nancy J. Cox, Christopher D. Brown, Paul Flicek, Ferran Reverter, Roderic Guigó, Tuuli Lappalainen, Sarah E. Gould, Deborah C. Mash, Michael T. Moser, Andrew B. Nobel, Takunda Matose, Jingchun Zhu, Joe R. Davis, Andrey A. Shabalin, Jie Quan, Pedro G. Ferreira, Taru Tukiainen, Ellen Gelfand, Cédric Howald, Buhm Han, Emily K. Tsang, Andrew P. Feinberg, Caroline Linke, Kane Hadley, Richard Sandstrom, Mark D. Johnson, Joshua M. Akey, Ian C. McDowell, Daniel R. Zerbino, Alexis Battle, Brian Roe, Daniel G. MacArthur, Ellen Karasik, Marcus Hunter, Anjené M. Addington, Thomas Juettemann, Konrad J. Karczewski, Duyen T. Nguyen, Lei Hou, Stephen B. Montgomery, YoSon Park, Nicole C. Lockart, Lin Chen, Rajinder Kaul, Ruiqi Jian, Robert G. Montroy, Xiao Li, Michael Snyder, Beryl B. Cummings, Kimberly M. Valentino, Ariel D. H. Gewirtz, François Aguet, Jeffrey McLean, Gary Walters, Farhad Hormozdiari, William F. Leinweber, Gad Getz, Jeffery P. Struewing, Anne Ndungu, Dan L. Nicolae, Benoit Molinie, Lihua Jiang, Michael Sammeth, W. James Kent, John Palowitch, Brian Craft, Donald F. Conrad, Kathryn Demanelis, Jason Bridge, Jin Billy Li, A. Roger Little, Nicholas Van Wittenberghe, Stephen J. Trevanion, Pejman Mohammadi, Michael S. Noble, Kate R. Rosenbloom, Marian S. Fernando, Benjamin J. Strober, Ping Guan, Brunilda Balliu, Yungil Kim, Kevin Myer, Christine B. Peterson, Pushpa Hariharan, Jae Hoon Sul, Abhi Rao, Michael F. Salvatore, Qin Li, Eun Yong Kang, Matthew T. Maurano, Ayellet V. Segrè, Dan Sheppard, Fred A. Wright, Matthew Stephens, Kasper D. Hansen, Chiara Sabatti, Kevin S. Smith, Xin Li, Ruth Barshir, Muhammad G. Kibriya, Farhan N. Damani, Manolis Kellis, Olivier Delaneau, Shin Lin, Richard Hasz, Michael J. Gloudemans, Anita H. Undale, Mary Goldman, Fidencio J. Neri, Katherine H. Huang, David E. Tabor, Manuel Muñoz-Aguirre, Maghboeba Mosavel, Simona Volpi, Latarsha J. Carithers, Anna M. Smith, Genna Gliner, Eleazar Eskin, Nikolaos I Panousis, Benedict Paten, Andrew A. Brown, Jessica Lin, Kieron Taylor, Robert E. Handsaker, Laura Barker, Casey Martin, Meng Wang, Farzana Jasmine, Scott D. Jewell, Nathan S. Abell, Kristin G. Ardlie, Shilpi Singh, Mary Barcus, Anthony Payne, Christopher Lee, Xiaoquan Wen, Nicola J. Rinaldi, Hua Tang, Yongjin Park, Christopher Johns, Saboor Shad, Judith B. Zaugg, Reza Sodaei, Maria M. Tomaszewski, David A. Davis, Joanne Chan, Laura A. Siminoff, Mark I. McCarthy, Ki Sung Um, Karna Robinson, Esti Yeger-Lotem, Martijn van de Bunt, Meritxell Oliva, Jemma Nelson, Negin Vatanian, Colby Chiang, Jeffrey A. Thomas, Alexandra J. Scott, Omer Basha, Jessica Halow, Panagiotis Papasaikas, Barbara A. Foster, Barbara E. Engelhardt, Sarah Kim-Hellmuth, Li Wang, Gireesh K. Bogu, Sandra Linder, Sarah Urbut, Ashis Saha, Gen Li, Bernadette Mestichelli, Chuan Gao, John A. Stamatoyannopoulos, Liqun Qi, Princy Parsana, Helen M. Moore, Gene Kopen, and GTEx, Consortium
Subjects: Gene isoform, 0301 basic medicine, Genotyping Techniques, Bioinformatics, RNA Splicing, 1.1 Normal biological development and functioning, Gene regulatory network, Method, Genomics, Computational biology, Biology, Medical and Health Sciences, GTEx Consortium, Transcriptome, 03 medical and health sciences, Databases, 0302 clinical medicine, Genetic, Transcription (biology), Underpinning research, Genetic variation, Gene expression, Genetics, Humans, ddc:576.5, Gene Regulatory Networks, Polymorphism, Gene, Genetics (clinical), 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Gene Expression Profiling, Human Genome, Bayes Theorem, Single Nucleotide, Biological Sciences, Gene expression profiling, 030104 developmental biology, Gene Expression Regulation, Organ Specificity, RNA splicing, RNA, Generic health relevance, Sequence Analysis, 030217 neurology & neurosurgery, Biotechnology
Abstract: Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of regulatory genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single or small sets of tissues. Here, we have reconstructed networks that capture a much more complete set of regulatory relationships, specifically including regulation of relative isoform abundance and splicing, and tissue-specific connections unique to each of a diverse set of tissues. Using the Genotype-Tissue Expression (GTEx) project v6 RNA-sequencing data across 44 tissues in 449 individuals, we evaluated shared and tissue-specific network relationships. First, we developed a framework called Transcriptome Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the complex interplay between the regulation of splicing and transcription. We built TWNs for sixteen tissues, and found that hubs with isoform node neighbors in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome, and providing a set of candidate shared and tissue-specific regulatory hub genes. Next, we used a Bayesian biclustering model that identifies network edges between genes with co-expression in a single tissue to reconstruct tissue-specific networks (TSNs) for 27 distinct GTEx tissues and for four subsets of related tissues. Using both TWNs and TSNs, we characterized gene co-expression patterns shared across tissues. Finally, we found genetic variants associated with multiple neighboring nodes in our networks, supporting the estimated network structures and identifying 33 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships between genes in the human transcriptome, including tissue-specificity of gene co-expression, regulation of splicing, and the coordinated impact of genetic variation on transcription.
Published: 2017

15. Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

Author: Zarko Manojlovic, Daniel C. Rohrer, Shukmei Wong, Megan Washington, Austin Christofferson, Daniel Auclair, Jonathan J Keats, John D. Carpten, Jessica Aldrich, Scott D. Jewell, Winnie S. Liang, Rick A. Kittles, David Craig, and Mary Derome
Subjects: Male, 0301 basic medicine, Cancer Research, Mutation rate, Gene Identification and Analysis, Plasma Cell Disorders, Hematologic Cancers and Related Disorders, White Blood Cells, Sequencing techniques, Mutation Rate, Animal Cells, Genotype, Medicine and Health Sciences, Ethnicities, Exome, Genome Sequencing, Mutation frequency, African American people, Genetics (clinical), Multiple myeloma, Oncogene Proteins, Genetics, Microfilament Proteins, High-Throughput Nucleotide Sequencing, RNA sequencing, Hematology, Population groupings, Middle Aged, Myelomas, Oncology, Interferon Regulatory Factors, Female, Cellular Types, Multiple Myeloma, Research Article, Adult, lcsh:QH426-470, Immune Cells, Plasma Cells, Immunology, Black People, Biology, Malignancy, White People, 03 medical and health sciences, Germline mutation, medicine, Point Mutation, Humans, Myelomas and Lymphoproliferative Diseases, Mutation Detection, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Blood Cells, Point mutation, Racial Groups, Cancers and Neoplasms, Biology and Life Sciences, Proteins, Cell Biology, medicine.disease, Research and analysis methods, Cytoskeletal Proteins, lcsh:Genetics, Molecular biology techniques, 030104 developmental biology, Mutation, Somatic Mutation, People and places, Tumor Suppressor Protein p53, Transcription Factors
Abstract: Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups. Of interest, BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations., Author summary This study represents the largest comprehensive molecular analysis of ethnically defined newly diagnosed treatment naïve Multiple Myeloma (MM). We revealed significant differences in mutation frequencies for important cancer genes between AA and CA MM. This study provides support for interrogating diverse tumor cohorts to best understand tumor genomics across populations.
Published: 2017

16. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans

Author: Mehran Taherian, Debra Bradbury, Emmanouil T. Dermitzakis, Manuel A. Rivas, Deborah C. Mash, Ayellet V. Segrè, Luan Lin, Ping Guan, Kimberly Ramsey, Mary Barcus, Deborah Colantuoni, Xiaoquan Wen, Julian Maller, Ferran Reverter, Laura A. Siminoff, Bryan Gillard, Dana R. Valley, Gen Li, Jeffery P. Struewing, Philip A. Branton, Roderic Guigó, Nancy Roche, Charles Shive, Christopher Choi, Johnell Fleming, Timothée Flutre, Latarsha J. Carithers, Taylor Young, Anuar Konkashbaev, Matthew Stephens, Daniel G. MacArthur, Rick Hasz, Mark I. McCarthy, Joel N. Hirschhorn, Sara Mostafavi, Lucas D. Ward, Amanda Brown, Ki Sung Um, Manolis Kellis, Robin Burges, Eric R. Gamazon, Heather M. Traino, Gary F. Temple, Karna Robinson, Leslie H. Sobin, Daphne Koller, Halit Ongen, Bernadette Mestichelli, John T. Lonsdale, Kimberly M. Valentino, Ellen Gelfand, David Tabor, Taru Tukiainen, Mike Salvatore, Gary Walters, Susan L. Sullivan, Jason Bridge, Carolyn C. Compton, Kenneth W. Hambright, Joy T. Boyer, Bin Zhang, Anita H. Undale, Michael Sammeth, Helen M. Moore, Nancy J. Cox, Andrey A. Shabalin, Kenyon Erickson, Nicole C. Lockhart, Gad Getz, Pushpa Hariharan, Benjamin Iriarte, Jakob M. Goldmann, Pouya Kheradpour, John Syron, Jimmie B. Vaught, Jun Zhu, Hae Kyung Im, Jean Monlong, John Seleski, Marta Melé, Edmund Lo, Yvonne Marcus, Pedro G. Ferreira, Stephen A. Buia, Liqun Qi, Greg E. Korzeniewski, Michael T. Moser, Ivan Rusyn, Andrew B. Nobel, Casandra A. Trowbridge, Timothy J. Sullivan, Chunrong Lu, Barbara A. Foster, Laura Barker, Jun Liu, Shenpei Wu, Anna M. Smith, Joanne P. Demchok, Dan L. Nicolae, Jeffrey A. Thomas, Jonathan K. Pritchard, Sherilyn Sawyer, Fred A. Wright, Wendy Winckler, Angela Britton, Zhidong Tu, Jorge Tejada, David S. DeLuca, Yi-Hui Zhou, Roger Little, Jeffrey McLean, Simona Volpi, Tõnu Esko, Kristin G. Ardlie, Monkol Lek, Daniel C. Rohrer, Susan E. Koester, Harold Magazine, Mark Miklos, Quan Long, Jialiang Yang, Cameron D. Palmer, Maghboeba Mosavel, Scott D. Jewell, Tuuli Lappalainen, Alexis Battle, Ellen Karasik, Margaret J. Basile, Saboor Shad, Denee Tidwell, Yan Meng, Chana A. Rabiner, Tao Huang, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), NIH, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: RNA, Untranslated, Genotype, RNA Splicing, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Blood Pressure, Pilot Projects, Quantitative trait locus, Biology, Expression quantitative trait loci, eQTL, Article, Human disease, Genotype-Tissue Expression, Genetic variation, Humans, Disease, Gene Regulatory Networks, Alleles, Biomedicine, Genetics, Regulation of gene expression, Multidisciplinary, Genome, Human, Sequence Analysis, RNA, business.industry, GTPase-Activating Proteins, Genetic Variation, Tibial Arteries, Gene Expression Regulation, Organ Specificity, Multigene Family, Transcriptome, business, Genome-Wide Association Study
Abstract: UMR AGAP - équipe DAAV (Diversité, adaptation et amélioration de la vigne)139 auteurs : Ardlie KG, Deluca DS, Segrè AV, Sullivan TJ, Young TR, Gelfand ET, Trowbridge CA, Maller JB, Tukiainen T, Lek M, Ward LD, Kheradpour P, Iriarte B, Meng Y, Palmer CD, Esko T, Winckler W, Hirschhorn JN, Kellis M, MacArthur DG, Getz G, Shabalin AA, Li G, Zhou YH, Nobel AB, Rusyn I, Wright FA, Lappalainen T, Ferreira PG, Ongen H, Rivas MA, Battle A, Mostafavi S, Monlong J, Sammeth M, Melé M, Reverter F, Goldmann JM, Koller D, Guigó R, McCarthy MI, Dermitzakis ET, Gamazon ER, Im HK, Konkashbaev A, Nicolae DL, Cox NJ, Flutre T, Wen X, Stephens M, Pritchard JK, Tu Z, Zhang B, Huang T, Long Q, Lin L, Yang J, Zhu J, Liu J, Brown A, Mestichelli B, Tidwell D, Lo E, Salvatore M, Shad S, Thomas JA, Lonsdale JT, Moser MT, Gillard BM, Karasik E, Ramsey K, Choi C, Foster BA, Syron J, Fleming J, Magazine H, Hasz R, Walters GD, Bridge JP, Miklos M, Sullivan S, Barker LK, Traino HM, Mosavel M, Siminoff LA, Valley DR, Rohrer DC, Jewell SD, Branton PA, Sobin LH, Barcus M, Qi L, McLean J, Hariharan P, Um KS, Wu S, Tabor D, Shive C, Smith AM, Buia SA, Undale AH, Robinson KL, Roche N, Valentino KM, Britton A, Burges R, Bradbury D, Hambright KW, Seleski J, Korzeniewski GE, Erickson K, Marcus Y, Tejada J, Taherian M, Lu C, Basile M, Mash DC, Volpi S, Struewing JP, Temple GF, Boyer J, Colantuoni D, Little R, Koester S, Carithers LJ, Moore HM, Guan P, Compton C, Sawyer SJ, Demchok JP, Vaught JB, Rabiner CA, Lockhart NC, Ardlie KG, Getz G, Wright FA, Kellis M, Volpi S, Dermitzakis ET.; Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of RNA sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by eQTLs. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues.
Published: 2015

17. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Author: Mark I. McCarthy, Joel N. Hirschhorn, Karna Robinson, Edmund Lo, Shenpei Wu, Stephen A. Buia, Jeffrey A. Thomas, David S. DeLuca, Francesca Petralia, Saboor Shad, Casandra A. Trowbridge, Simona Volpi, Debra Bradbury, Gad Getz, Zhidong Tu, Jialiang Yang, Magboeba Mosavel, Eric R. Gamazon, Carmen Argmann, Tuuli Lappalainen, Rick Hasz, Kimberly Ramsey, Deborah Colantuoni, Xiaoquan Wen, Nicole C. Lockhart, Gary F. Temple, Margaret J. Basile, Jonathan K. Pritchard, Julian Maller, Monkol Lek, Alexis Battle, Ellen Gelfand, Bryan Gillard, Dana R. Valley, Quan Long, Ellen Karasik, Anna M. Smith, Roderic Guigó, Daphne Koller, Halit Ongen, John T. Lonsdale, Daniel C. Rohrer, Helen M. Moore, Kristin G. Ardlie, Charles Shive, Ping Guan, Charles V. Mobbs, Taru Tukiainen, Nancy Roche, Taylor Young, Philip A. Branton, Anuar Konkashbaev, Matthew Stephens, Fred A. Wright, Gary Walters, Amanda M. V. Brown, Pedro G. Ferreira, Christopher Choi, Denee Tidwell, Greg E. Korzeniewski, Lucas D. Ward, Andrey A. Shablin, Scott Jewel, Manuel A. Rivas, Yan Meng, Timothée Flutre, Pushpa Hariharan, Deborah C. Mash, Susan E. Koester, John Seleski, Johnelle Fleming, Susan L. Sullivan, Kimberly M. Valentino, Yi-Hui Zhou, Harold Magazine, Latarsha J. Carithers, Jorge Tejada, Daniel G. MacArthur, Mark Miklos, Dan L. Nicolae, Chana A. Rabiner, Roger Little, Nancy J. Cox, Pouya Kheradpour, Jeff Struewing, Barnaby E. Robles, Sara Mostafavi, Yong Zhao, Kenneth W. Hambright, Michael Sammeth, Sherilyn Sawyer, Joy T. Boyer, Manolis Kellis, Robin Burges, Mike Salvatore, Wendy Winckler, Angela Britton, Gen Li, Cameron D. Palmer, Jason Bridge, Tao Huang, Laura Barker, Emmanouil T. Dermitzakis, Mehran Taherian, Ayellet V. Segrè, Luan Lin, Laura A. Siminoff, Ferran Reverter, John Syron, Jimmie B. Vaught, Jun Zhu, Bin Zhang, Benjamin Iriarte, Jean Monlong, Jakob Goldman, Marta Melé, Michael T. Moser, Ivan Rusyn, Andrew B. Nobel, Timothy J. Sullivan, Heather M. Traino, Carolyn C. Compton, Chunrong Lu, Jun Liu, Anita H. Undale, Kenyon Erickson, Eric E. Schadt, Leslie H. Sobin, Bernadette Mestichelli, David Tabor, Yvonne Marcus, Liqun Qi, Barbara A. Foster, Joanne P. Demchok, Dermitzakis, Emmanouil, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Ward, Lucas D., Kheradpour, Pouya, Iriarte, Benjamin, and Kellis, Manolis
Subjects: Adult, Male, Systems biology, Gene Expression, Computational biology, Biology, medicine.disease_cause, Biologia computacional, Article, Organ Specificity/genetics, Transcriptome, 03 medical and health sciences, Mice, Young Adult, 0302 clinical medicine, Gene expression, medicine, Aging/genetics, Animals, Cluster Analysis, Humans, ddc:576.5, Gene, Genetic Association Studies, 030304 developmental biology, Aged, Genetics, Regulation of gene expression, 0303 health sciences, Mutation, Multidisciplinary, Gene Expression Profiling, Molecular Sequence Annotation, Computational Biology/methods, Middle Aged, 3. Good health, Gene expression profiling, Gene Expression Regulation, Female, Organ Specificity, 030217 neurology & neurosurgery
Abstract: Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger “co-aging” than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases., National Cancer Institute (U.S.), National Human Genome Research Institute (U.S.), National Heart, Lung, and Blood Institute, National Institute on Drug Abuse (NIDA), National Institute of Mental Health (U.S.), National Institute of Neurological Disorders and Stroke (U.S.)
Published: 2015

18. Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases

Author: Gajanan Nilaver, Curtis A. Machida, P Kirigiti, Daniel C. Rohrer, H V Nichols, T C Wyman, and K Y Pilcher
Subjects: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Genetic enhancement, Central nervous system, Endothelial Growth Factors, Cell Line, Fetal Tissue Transplantation, Neurotrophic factors, Internal medicine, Nerve Growth Factor, Genetics, medicine, Animals, Humans, Brain Tissue Transplantation, Promoter Regions, Genetic, Molecular Biology, Lymphokines, Vascular Endothelial Growth Factors, business.industry, Genetic transfer, Gene Transfer Techniques, Brain, Neurodegenerative Diseases, Genetic Therapy, medicine.disease, Carcinoembryonic Antigen, Transplantation, Endocrinology, medicine.anatomical_structure, Nerve growth factor, Lac Operon, Peripheral nervous system, Cancer research, Molecular Medicine, Metallothionein, Alzheimer's disease, business
Abstract: Genetic transfer approaches have received recent consideration as potential treatment modalities for human central and peripheral nervous system (CNS and PNS, respectively) neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Transplantation of genetically modified cells into the brain represents a promising strategy for the delivery and expression of specific neurotrophic factors, neurotransmitter-synthesizing enzymes, and cellular regulatory proteins for intervention in neurodegenerative diseases. The use of specific regulatable promoters may also provide potential control of gene expression required for dose-specific or time-specific therapeutic strategies. In this article, we review the potential use of activated promoters in ex vivo systems for the potential genetic therapy of neurodegenerative disorders, and then describe our own studies using the zinc-inducible metallothionein promoter for the regulated expression of nerve growth factor (NGF) in rodent brain transplants.
Published: 1999

19. The Genotype-Tissue Expression (GTEx) project

Author: Mark S. Guyer, Mark I. McCarthy, Assya Abdallah, Bree Berghuis, Fernando U. Garcia, Manolis Kellis, Robin Burges, Karna Robinson, Jeffery P. Struewing, Daphne Koller, John T. Lonsdale, Leslie Derr, Roger Little, Bryan Gillard, Edmund Lo, Penelope Williams, Sara Mostafavi, Deborah C. Mash, Gary Walters, Johnelle Fleming, Alexander Thomson, David S. DeLuca, Norma Diaz-Mayoral, Timothée Flutre, Kevin Groch, MacArthur Daniel MacArthur, Zhidong Tu, Jean Monlong, Eric R. Gamazon, Steve Buia, Gary F. Temple, Susan E. Koester, Manual Rivas, Matthew Stevens, Saboor Shad, Wendy Winckler, Patrick Bender, Charles Shive, Harold Magazine, Ellen Gelfand, Helen F. Moore, Mike Moser, Nancy Young, Dan Maxim, Ivan Rusyn, Nataliya Sharopova, Andrew B. Nobel, Anuar Konkashbaev, Richard Hasz, David Tabor, Thomas R. Insel, Leslie H. Sobin, Jun Liu, Eric D. Green, Deborah Colantuoni, Xiaoquan Wen, Kenyon Erickson, Mike Feolo, Mike Salvatore, George B. Grant, Kim Valentino, Eddie Cortadillo, Yvonne Marcus, Julian Maller, Sreenath Nampally, Anne Sturcke, John Syron, Jimmie B. Vaught, Jun Zhu, Hae Kyung Im, Liqun Qi, Mark Cosentino, Heather M. Traino, Thomas Lehner, Jason Bridge, Carolyn C. Compton, Barbara A. Foster, Michael Sammeth, Nicole C. Lockhart, Alexis Battle, Kimberley Ramsey, Laura A. Siminoff, Gad Getz, Joanne P. Demchok, Mary Kennedy, Justin Paschal, Angela Zimmerman, Kristin Feenstra, Ellen Karasik, Laura Barker, Jonathan K. Pritchard, Elizabeth J. Thomson, Deborah Bradbury, Molly Donovan, Yin Yao, Kristin G. Ardlie, Philip Harbach, Daniel C. Rohrer, Eric Hudson, James A. Robb, Roderic Guigó, Taylor Young, Elizabeth L. Wilder, Rebecca Phillips, Nancy J. Cox, Andrey A. Shabalin, Phillip Branton, Susan L. Sullivan, James M. Anderson, Fred A. Wright, Simona Volpi, Joy T. Boyer, Cathy Ng, Emmanouil T. Dermitzakis, Tuuli Lappalainen, Margaret J. Basile, Maghboeba Mosavel, Jeffrey Thomas, Scott D. Jewell, Yan Meng, Dana Filkins, Dan L. Nicolae, Lisa Turner, Sherilyn Sawyer, Anna M. Smith, Greg E. Korzeniewski, Theresa Engel, National Disease Research Interchange, Building Research Establishment (BRE/Edinburgh), University of Edinburgh, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), NIH, Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, codage des protéines, Quantitative Trait Loci, Gene Expression, Médecine humaine et pathologie, Tissue Banks, Biology, Bioinformatics, Article, 03 medical and health sciences, 0302 clinical medicine, Genotype-Tissue Expression, Genetic variation, Gene expression, Genetics, Humans, Genomes, 030304 developmental biology, Genetic association, 0303 health sciences, Gene Expression Profiling, Molecular Sequence Annotation, étude d'association pangénomique, Expressió gènica, United States, 3. Good health, Agricultural sciences, Consensus Development Conferences, NIH as Topic, Government Programs, Santé publique et épidémiologie, phénotype, Underlying disease, Organ Specificity, Regulatory sequence, Tissue bank, Expression quantitative trait loci, Human health and pathology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030217 neurology & neurosurgery, Sciences agricoles, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract: Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues., National Institutes of Health (U.S.) (US NIH to the Broad Institute of Harvard and MIT, R01 DA006227-17), National Institute of Drug Abuse, National Institute of Mental Health (U.S.), National Institute of Neurological Disorders and Stroke (U.S.)
Published: 2013

20. Cancer and Leukemia Group B Pathology Committee guidelines for tissue microarray construction representing multicenter prospective clinical trial tissues

Author: Jonathan F. Lara, Frederic M. Waldman, Gloria Broadwater, Baljit Singh, Sunil Badve, Scott D. Jewell, Ann D. Thor, Beiyun Chen, Ira J. Bleiweiss, Torsten O. Nielsen, David L. Rimm, Kisha A. Mitchell, Anthony M. Magliocco, Gregory J. Tsongalis, Daniel C. Rohrer, Donald A. Berry, Peter M. Ravdin, Wendy L. Frankel, Eric D. Hsi, and Richard L. Schilsky
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Clinical Trials as Topic, Tissue microarray, business.industry, MEDLINE, Cancer, Anatomical pathology, medicine.disease, Specimen Handling, Clinical trial, Special Article, Oncology, Tissue Array Analysis, medicine, Biomarkers, Tumor, Biomarker (medicine), Population study, Humans, Multicenter Studies as Topic, business, Companion diagnostic
Abstract: Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups. A principal goal is to maximize the number of assays with this precious tissue. However, production strategies for these arrays have not been standardized, possibly decreasing the value of the study. In this article, members of the Cancer and Leukemia Group B Pathology Committee relay our experiences as array facility directors and propose guidelines regarding the production of high-quality TMAs for cooperative group studies. We also discuss statistical issues arising from having a proportion of patients available for TMAs and the possibility that patients with TMAs fail to represent the greater study population.
Published: 2011

21. Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors

Author: Richard M. Weinshilboum, Gregory D. Jenkins, Daniel J. Schaid, Matthew P. Goetz, Matthew J. Ellis, Judy Anne W. Chapman, Anthony Batzler, Liewei Wang, Joseph L. Pater, Mohan Liu, Michiaki Kubo, Vered Stearns, Lois E. Shepherd, Taisei Mushiroda, James N. Ingle, David A. Flockhart, Kathleen I. Pritchard, Yusuke Nakamura, Daniel C. Rohrer, and Paul E. Goss
Subjects: Oncology, Cancer Research, Pathology, Genome-wide association study, Severity of Illness Index, chemistry.chemical_compound, Exemestane, Aromatase, Musculoskeletal System, Randomized Controlled Trials as Topic, Aged, 80 and over, Receptors, Interleukin-17, biology, Aromatase Inhibitors, Chromosome Mapping, Common Terminology Criteria for Adverse Events, Middle Aged, Gene Expression Regulation, Neoplastic, Postmenopause, Female, medicine.drug, medicine.medical_specialty, Genotype, Anastrozole, Antineoplastic Agents, Breast Neoplasms, Polymorphism, Single Nucleotide, Internal medicine, Proto-Oncogene Proteins, Original Reports, Nitriles, medicine, Humans, Adverse effect, Aged, Neoplasm Staging, Retrospective Studies, Chromosomes, Human, Pair 14, business.industry, Case-control study, Estrogens, Triazoles, Clinical trial, Androstadienes, Logistic Models, chemistry, Clinical Trials, Phase III as Topic, Case-Control Studies, biology.protein, business, Genome-Wide Association Study
Abstract: Purpose We performed a case-control genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with musculoskeletal adverse events (MS-AEs) in women treated with aromatase inhibitors (AIs) for early breast cancer. Patients and Methods A nested case-control design was used to select patients enrolled onto the MA.27 phase III trial comparing anastrozole with exemestane. Cases were matched to two controls and were defined as patients with grade 3 or 4 MS-AEs (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0) or those who discontinued treatment for any grade of MS-AE within the first 2 years. Genotyping was performed with the Illumina Human610-Quad BeadChip. Results The GWAS included 293 cases and 585 controls. A total of 551,358 SNPs were analyzed, followed by imputation and fine mapping of a region of interest on chromosome 14. Four SNPs on chromosome 14 had the lowest P values (2.23E-06 to 6.67E-07). T-cell leukemia 1A (TCL1A) was the gene closest (926-7000 bp) to the four SNPs. Functional genomic studies revealed that one of these SNPs (rs11849538) created an estrogen response element and that TCL1A expression was estrogen dependent, was associated with the variant SNP genotypes in estradiol-treated lymphoblastoid cells transfected with estrogen receptor alpha and was directly related to interleukin 17 receptor A (IL17RA) expression. Conclusion This GWAS identified SNPs associated with MS-AEs in women treated with AIs and with a gene (TCL1A) which, in turn, was related to a cytokine (IL17). These findings provide a focus for further research to identify patients at risk for MS-AEs and to explore the mechanisms for these adverse events.
Published: 2010

22. Intraspinal extradural meningeal cyst demonstrating ball-valve mechanism of formation. Case report

Author: Daniel C. Rohrer, Kim J. Burchiel, and David P. Gruber
Subjects: Dorsum, Adult, Male, medicine.medical_specialty, Dura mater, medicine.medical_treatment, Spinal Cord Diseases, Spinal cord compression, medicine, Humans, Cyst, business.industry, Cysts, Thoracolumbar Region, Meningeal cyst, Anatomy, Spinal cord, Marsupialization, medicine.disease, Surgery, body regions, medicine.anatomical_structure, Dura Mater, business, Spinal Nerve Roots, human activities, Spinal Cord Compression
Abstract: ✓ A diverse collection of unverified theories as to the etiology of extradural meningeal cysts have been previously proposed. One case of intraspinal extradural meningeal cyst of the thoracolumbar region is presented in which a ball-valve mechanism involving an idiopathic dural rent and a herniated segment of an underlying dorsal rootlet was suggested by the operative findings. Closure of the dural rent with marsupialization of the meningeal cyst obliterated this extradural lesion. The ball-valve mechanism of formation and other previously proposed theories are discussed.
Published: 1993

23. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics

Author: Barbara E. Engelhardt, Sarah Kim-Hellmuth, Sarah Urbut, Ashis Saha, Gen Li, Jessica Halow, Panagiotis Papasaikas, Simona Volpi, Alvaro N. Barbeira, Jared L. Nedzel, Meng Wang, Nikolaos I Panousis, Benedict Paten, Lori E. Brigham, Gao Wang, Mary Barcus, Anthony Payne, Xiaoquan Wen, Nicola J. Rinaldi, Hua Tang, Seva Kashin, Casey Martin, Steven Hunter, Yi-Hui Zhou, Kristen Lee, Ian C. McDowell, Jason M. Torres, Alexandra J. Scott, Kane Hadley, Duyen T. Nguyen, Leslie H. Sobin, Jiamao Zheng, Paul Flicek, Casandra A. Trowbridge, Anjené M. Addington, Omer Basha, Brandon L. Pierce, Pejman Mohammadi, Xiao Li, Halit Ongen, Ki Sung Um, John T. Lonsdale, Alexis Battle, Takunda Matose, Kathryn Demanelis, Yuan He, Bernadette Mestichelli, Kasper D. Hansen, Marcus Hunter, Shin Lin, Richard Hasz, Thomas Juettemann, Ellen Karasik, Taru Tukiainen, Lin Chen, Fred A. Wright, Martijn van de Bunt, Meritxell Oliva, Fidencio J. Neri, François Aguet, Todd L. Edwards, Judith B. Zaugg, Michael Snyder, Gary Walters, Yongjin Park, Mary Goldman, Michael Sammeth, Kristin G. Ardlie, A. Roger Little, Reza Sodaei, Stephen J. Trevanion, Kevin S. Smith, Stephen B. Montgomery, Katherine H. Huang, John A. Stamatoyannopoulos, David E. Tabor, Gene Kopen, Melina Claussnitzer, Nancy Roche, Rodrigo Bonazzola, Deborah C. Mash, Helen M. Moore, Anne Ndungu, Lihua Jiang, Konrad J. Karczewski, Marian S. Fernando, Liqun Qi, Princy Parsana, Ping Guan, Eleazar Eskin, Kate R. Rosenbloom, Jason Bridge, Maria M. Tomaszewski, David A. Davis, Joseph Wheeler, Sarah E. Gould, Morgan Diegel, Eric S. Torstenson, Nancy J. Cox, Daniel R. Zerbino, Joshua M. Akey, Kimberly M. Valentino, Brunilda Balliu, Jingchun Zhu, Joe R. Davis, Nicholas Van Wittenberghe, Michael F. Salvatore, Susan E. Koester, Barbara A. Foster, Andrey A. Shabalin, Ira M. Hall, John Vivian, Eun Yong Kang, Nathan S. Abell, Laure Fresard, Lindsay F. Rizzardi, Ayellet V. Segrè, Dan Sheppard, Rajinder Kaul, Jeffrey McLean, Michael Washington, Joanne Chan, Mark Miklos, Benoit Molinie, Christopher Johns, Laura M. Huckins, Monkol Lek, Christopher D. Brown, Laura A. Siminoff, Alisa McDonald, Abhi Rao, Jean Monlong, Jie Quan, Diego Garrido-Martín, Barbara E. Stranger, Donald F. Conrad, Farhan N. Damani, Cédric Howald, Buhm Han, Michael S. Noble, Caroline Linke, Daniel C. Rohrer, Jimmie B. Vaught, Hae Kyung Im, Audra K. Johnson, Rui Zhang, Muhammad G. Kibriya, Matthew Stephens, Chiara Sabatti, Brian Roe, Latarsha J. Carithers, Robert E. Handsaker, Pushpa Hariharan, Boxiang Liu, Manolis Kellis, YoSon Park, Manuel Muñoz-Aguirre, Lei Hou, Matthew T. Maurano, Ariel D. H. Gewirtz, Ruth Barshir, Michael J. Gloudemans, Li Wang, Gireesh K. Bogu, Christopher Lee, Anita H. Undale, Genna Gliner, Sandra Linder, Serghei Mangul, Andrew A. Brown, Tzintzuni Garcia, Eric Haugen, Michael T. Moser, Jessica Lin, Andrew B. Nobel, Richard Sandstrom, Emmanouil T. Dermitzakis, Kieron Taylor, Brian Jo, Rachna Kumar, Laura Barker, Magali Ruffier, Ferran Reverter, Saboor Shad, Jin Billy Li, Eli A. Stahl, Mark I. McCarthy, William F. Leinweber, Gad Getz, Karna Robinson, Xin Li, Esti Yeger-Lotem, Jemma Nelson, Negin Vatanian, Scott P. Dickinson, Colby Chiang, Jeffrey A. Thomas, Kaanan P. Shah, Maximilian Haeussler, Heather M. Traino, Concepcion R. Nierras, Fan Wu, Hualin S. Xi, Yaping Liu, Daniel Bates, Peter Hickey, Eric R. Gamazon, Jennifer A. Doherty, Ellen Gelfand, Jae Hoon Sul, Jeffery P. Struewing, Beryl B. Cummings, W. James Kent, John Palowitch, Brian Craft, Anna M. Smith, Pedro G. Ferreira, Emily K. Tsang, Andrew P. Feinberg, Nicole C. Lockart, Ruiqi Jian, Robert G. Montroy, Dan L. Nicolae, Yungil Kim, Kevin Myer, Christine B. Peterson, Benjamin J. Strober, Andrew D. Skol, Qin Li, Bryan Gillard, Dana R. Valley, Zachary Zappala, Philip A. Branton, Stephane E. Castel, Daniel G. MacArthur, Mark H. Johnson, Olivier Delaneau, Maghboeba Mosavel, Roderic Guigó, Farzana Jasmine, Scott D. Jewell, Shilpi Singh, Tuuli Lappalainen, Farhad Hormozdiari, and Heather E. Wheeler
Subjects: 0301 basic medicine, Science, Quantitative Trait Loci, Gene Expression, General Physics and Astronomy, Genome-wide association study, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Genome-wide association studies, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Meta-Analysis as Topic, Genetic variation, Humans, Computer Simulation, lcsh:Science, Gene, Genetics, Multidisciplinary, Models, Genetic, Chromosome Mapping, Genetic Variation, Tissue-Specific Gene Expression, Robustness (evolution), General Chemistry, Phenotype, 030104 developmental biology, Organ Specificity, Trait, lcsh:Q, Data integration, Genome-Wide Association Study
Abstract: Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes., Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

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23 results on '"Daniel C. Rohrer"'

1. Proteogenomic Characterization of Pancreatic Ductal Adenocarcinoma

2. Small Nucleolar RNA Score: An Assay to Detect Formalin-Overfixed Tissue

3. Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry

4. Proteogenomic and metabolomic characterization of human glioblastoma

5. A proteogenomic portrait of lung squamous cell carcinoma

6. A vast resource of allelic expression data spanning human tissues

7. Great Lakes Biorepository Research Network's Annual Biobanking Symposium: A Focus on Precision Medicine

8. Cold Ischemia Score: An mRNA Assay for the Detection of Extended Cold Ischemia in Formalin-Fixed, Paraffin-Embedded Tissue

9. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

10. Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

11. A Quantitative Proteome Map of the Human Body

12. Proteogenomic Characterization of Endometrial Carcinoma

13. Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

14. Co-expression networks reveal the tissue-specific regulation of transcription and splicing

15. Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

16. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans

17. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

18. Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases

19. The Genotype-Tissue Expression (GTEx) project

20. Cancer and Leukemia Group B Pathology Committee guidelines for tissue microarray construction representing multicenter prospective clinical trial tissues

21. Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors

22. Intraspinal extradural meningeal cyst demonstrating ball-valve mechanism of formation. Case report

23. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics

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23 results on '"Daniel C. Rohrer"'

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