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1. Packaging, containerization, and virtualization of computational omics methods: Advances, challenges, and opportunities

Author

Alser, Mohammed, Waymost, Sharon, Ayyala, Ram, Lawlor, Brendan, Abdill, Richard J., Rajkumar, Neha, LaPierre, Nathan, Brito, Jaqueline, Ribeiro-dos-Santos, Andre M., Firtina, Can, Almadhoun, Nour, Sarwal, Varuni, Eskin, Eleazar, Hu, Qiyang, Strong, Derek, Byoung-Do, Kim, Abedalthagafi, Malak S., Mutlu, Onur, and Mangul, Serghei

Subjects
Quantitative Biology - Genomics, Computer Science - Distributed, Parallel, and Cluster Computing, Computer Science - Software Engineering, Statistics - Applications
Abstract

Omics software tools have reshaped the landscape of modern biology and become an essential component of biomedical research. The increasing dependence of biomedical scientists on these powerful tools creates a need for easier installation and greater usability. Packaging, virtualization, and containerization are different approaches to satisfy this need by wrapping omics tools in additional software that makes the omics tools easier to install and use. Here, we systematically review practices across prominent packaging, virtualization, and containerization platforms. We outline the challenges, advantages, and limitations of each approach and some of the most widely used platforms from the perspectives of users, software developers, and system administrators. We also propose principles to make packaging, virtualization, and containerization of omics software more sustainable and robust to increase the reproducibility of biomedical and life science research.

Published
2022

3. Unlocking capacities of genomics for the COVID-19 response and future pandemics

Author

Knyazev, Sergey, Chhugani, Karishma, Sarwal, Varuni, Ayyala, Ram, Singh, Harman, Karthikeyan, Smruthi, Deshpande, Dhrithi, Baykal, Pelin Icer, Comarova, Zoia, Lu, Angela, Porozov, Yuri, Vasylyeva, Tetyana I, Wertheim, Joel O, Tierney, Braden T, Chiu, Charles Y, Sun, Ren, Wu, Aiping, Abedalthagafi, Malak S, Pak, Victoria M, Nagaraj, Shivashankar H, Smith, Adam L, Skums, Pavel, Pasaniuc, Bogdan, Komissarov, Andrey, Mason, Christopher E, Bortz, Eric, Lemey, Philippe, Kondrashov, Fyodor, Beerenwinkel, Niko, Lam, Tommy Tsan-Yuk, Wu, Nicholas C, Zelikovsky, Alex, Knight, Rob, Crandall, Keith A, and Mangul, Serghei

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Networking and Information Technology R&D (NITRD), Vaccine Related, Infectious Diseases, Emerging Infectious Diseases, Biotechnology, Prevention, Biodefense, Generic health relevance, Infection, Good Health and Well Being, COVID-19, Genomics, Humans, Pandemics, SARS-CoV-2, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

During the COVID-19 pandemic, genomics and bioinformatics have emerged as essential public health tools. The genomic data acquired using these methods have supported the global health response, facilitated development of testing methods, and allowed timely tracking of novel SARS-CoV-2 variants. Yet the virtually unlimited potential for rapid generation and analysis of genomic data is also coupled with unique technical, scientific, and organizational challenges. Here, we discuss the application of genomic and computational methods for the efficient data driven COVID-19 response, advantages of democratization of viral sequencing around the world, and challenges associated with viral genome data collection and processing.

Published
2022

4. Diversity in immunogenomics: the value and the challenge

Author

Peng, Kerui, Safonova, Yana, Shugay, Mikhail, Popejoy, Alice, Rodriguez, Oscar, Breden, Felix, Brodin, Petter, Burkhardt, Amanda M., Bustamante, Carlos, Cao-Lormeau, Van-Mai, Corcoran, Martin M., Duffy, Darragh, Guajardo, Macarena Fuentes, Fujita, Ricardo, Greiff, Victor, Jonsson, Vanessa D., Liu, Xiao, Quintana-Murci, Lluis, Rossetti, Maura, Xie, Jianming, Yaari, Gur, Zhang, Wei, Abedalthagafi, Malak S., Adekoya, Khalid O., Ahmed, Rahaman A., Chang, Wei-Chiao, Gray, Clive, Nakamura, Yusuke, Lees, William D., Khatri, Purvesh, Alachkar, Houda, Scheepers, Cathrine, Watson, Corey T., Hedestam, Gunilla B. Karlsson, and Mangul, Serghei

Subjects
Quantitative Biology - Genomics
Abstract

With the advent of high-throughput sequencing technologies, the fields of immunogenomics and adaptive immune receptor repertoire research are facing both opportunities and challenges. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become an increasingly important tool to characterize T and B cell responses in settings of interest. However, the majority of AIRR-seq studies conducted so far were performed in individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations and limiting their applications. As AIRR-seq studies depend on the ability to assign VDJ sequence reads to the correct germline gene segments, efforts to characterize the genomic loci that encode adaptive immune receptor genes in different populations are urgently needed. The availability of comprehensive germline gene databases and further applications of AIRR-seq studies to individuals of non-European ancestry will substantially enhance our understanding of human adaptive immune responses, promote the development of effective diagnostics and treatments, and eventually advance precision medicine., Comment: 22 pages,1 table

Published
2020

7. Fusing Peptide Epitopes for Advanced Multiplex Serological Testing for SARS-CoV-2 Antibody Detection

Author

Aldoukhi, Ali H., primary, Bilalis, Panayiotis, additional, Alhattab, Dana M., additional, Valle-Pérez, Alexander U., additional, Susapto, Hepi H., additional, Pérez-Pedroza, Rosario, additional, Backhoff-García, Emiliano, additional, Alsawaf, Sarah M., additional, Alshehri, Salwa, additional, Boshah, Hattan, additional, Alrashoudi, Abdulelah A., additional, Aljabr, Waleed A., additional, Alaamery, Manal, additional, Alrashed, May, additional, Hasanato, Rana M., additional, Farzan, Raed A., additional, Alsubki, Roua A., additional, Moretti, Manola, additional, Abedalthagafi, Malak S., additional, and Hauser, Charlotte A. E., additional

Published
2023
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8. Rigorous benchmarking of T-cell receptor repertoire profiling methods for cancer RNA sequencing

Author

Peng, Kerui, primary, Nowicki, Theodore S, additional, Campbell, Katie, additional, Vahed, Mohammad, additional, Peng, Dandan, additional, Meng, Yiting, additional, Nagareddy, Anish, additional, Huang, Yu-Ning, additional, Karlsberg, Aaron, additional, Miller, Zachary, additional, Brito, Jaqueline, additional, Nadel, Brian, additional, Pak, Victoria M, additional, Abedalthagafi, Malak S, additional, Burkhardt, Amanda M, additional, Alachkar, Houda, additional, Ribas, Antoni, additional, and Mangul, Serghei, additional

Published
2023
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9. GWAS and meta-analysis identifies 49 genetic variants underlying critical Covid-19

Author

Pairo-Castineira, Erola, Rawlik, Konrad, Bretherick, Andrew D, Qi, Ting, Wu, Yang, Nassiri, Isar, McConkey, Glenn A., Zechner, Marie, Klaric, Lucija, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Richmond , Anne, Millar, Jonathan, Russell, Clark D, Malinauskas, Tomas, Thwaites, Ryan, Morrice, Kirstie, Keating, Sean, Maslove, David M, Nichol, Alistair D, Semple, Malcolm Gracie, Knight, Julian, Shankar-Hari, Manu, Summers, Charlotte, Hinds , Charles, Horby, Peter, Ling, Lowell, McAuley, Danny F., Montgomery, Hugh, Openshaw, Peter J.M., Begg, Colin, Walsh, Timothy S., Tenesa, Albert, Flores, Carlos, Riancho, Jose A., Rojas-Martinez, Augusto, Lapunzina, Pablo, Yang, Jian, Ponting, Chris P, Wilson, James F, Vitart, Veronique, Abedalthagafi, Malak S, Luchessi, Andre, Parra, Esteban J, Cruz, Raquel, Carracedo, Angel, Fawkes, Angie, Murphy, Lee, Rowan, Kathy, Pereira, Alexandre C, Law, Andy, Fairfax, Benjamin P, Clohisey Hendry, Sara, and Baillie, J Kenneth

Subjects
Phenotype, Genetic Variation/genetics, Genotype, Genotyping Techniques, Whole Genome Sequencing, Monocytes/metabolism, Critical Illness, Genetic Predisposition to Disease/genetics, rab GTP-Binding Proteins/genetics, Humans, Transcriptome, COVID-19/genetics, Genome-Wide Association Study
Abstract

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Published
2023

10. Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative

Author

Guillaume, Butler-Laporte, Gundula, Povysil, Kosmicki, Jack A., Cirulli, Elizabeth T., Theodore, Drivas, Furini, Simone, Chadi, Saad, Axel, Schmidt, Pawel, Olszewski, Urszula, Korotko, Mathieu, Quinodoz, Elifnaz, Çelik, Kousik, Kundu, Klaudia, Walter, Junghyun, Jung, Stockwell, Amy D., Sloofman, Laura G., Jordan, Daniel M., Thompson, Ryan C., Diane Del Valle, Nicole, Simons, Esther, Cheng, Robert, Sebra, Schadt, Eric E., Seunghee, Kim-Schulze, Sacha, Gnjatic, Miriam, Merad, Buxbaum, Joseph D., Beckmann, Noam D., Charney, Alexander W., Bartlomiej, Przychodzen, Timothy, Chang, Pottinger, Tess D., Ning, Shang, Fabian, Brand, Fava, Francesca, Mari, Francesca, Karolina, Chwialkowska, Magdalena, Niemira, Szymon, Pula, J Kenneth Baillie, Alex, Stuckey, Antonio, Salas, Xabier, Bello, Jacobo, Pardo-Seco, Alberto, Gómez-Carballa, Irene, Rivero-Calle, Federico, Martinón-Torres, Andrea, Ganna, Karczewski, Konrad J., Kumar, Veerapen, Mathieu, Bourgey, Guillaume, Bourque, Robert JM Eveleigh, Vincenzo, Forgetta, David, Morrison, David, Langlais, Mark, Lathrop, Vincent, Mooser, Tomoko, Nakanishi, Robert, Frithiof, Michael, Hultström, Miklos, Lipcsey, Yanara, Marincevic-Zuniga, Jessica, Nordlund, Schiabor Barrett, Kelly M., William, Lee, Alexandre, Bolze, Simon, White, Stephen, Riffle, Francisco, Tanudjaja, Efren, Sandoval, Iva, Neveux, Shaun, Dabe, Nicolas, Casadei, Susanne, Motameny, Manal, Alaamery, Salam, Massadeh, Nora, Aljawini, Almutairi, Mansour S., Arabi, Yaseen M., Alqahtani, Saleh A., Al Harthi, Fawz S., Amal, Almutairi, Fatima, Alqubaishi, Sarah, Alotaibi, Albandari, Binowayn, Alsolm, Ebtehal A., Hadeel El Bardisy, Mohammad, Fawzy, Fang, Cai, Nicole, Soranzo, Adam, Butterworth, COVID-19 Host Genetics Initiative, DeCOI Host Genetics Group, GEN-COVID Multicenter Study (Italy), Daga, Sergio, Meloni, Ilaria, Mount Sinai Clinical Intelligence Center, GEN-COVID consortium (Spain), Genomicc, Consortium, Japan COVID-19 Task Force, Regeneron Genetics Center, Geschwind, Daniel H., Stephanie, Arteaga, Alexis, Stephens, Butte, Manish J., Boutros, Paul C., Yamaguchi, Takafumi N., Shu, Tao, Stefan, Eng, Timothy, Sanders, Tung, Paul J., Broudy, Michael E., Pan, Yu, Alfredo, Gonzalez, Nikhil, Chavan, Ruth, Johnson, Bogdan, Pasaniuc, Brian, Yaspan, Sandra, Smieszek, Carlo, Rivolta, Stephanie, Bibert, Pierre-Yves, Bochud, Maciej, Dabrowski, Pawel, Zawadzki, Mateusz, Sypniewski, Elżbieta, Kaja, Pajaree, Chariyavilaskul, Voraphoj, Nilaratanakul, Nattiya, Hirankarn, Vorasuk, Shotelersuk, Monnat, Pongpanich, Chureerat, Phokaew, Wanna, Chetruengchai, Katsushi, Tokunaga, Masaya, Sugiyama, Yosuke, Kawai, Takanori, Hasegawa, Tatsuhiko, Naito, Namkoong, Ho, Ryuya, Edahiro, Akinori, Kimura, Seishi, Ogawa, Takanori, Kanai, Koichi, Fukunaga, Yukinori, Okada, Seiya, Imoto, Satoru, Miyano, Serghei, Mangul, Abedalthagafi, Malak S., Hugo, Zeberg, Grzymski, Joseph J., Washington, Nicole L., Stephan, Ossowski, Ludwig, Kerstin U., Schulte, Eva C., Olaf, Riess, Marcin, Moniuszko, Miroslaw, Kwasniewski, Hamdi, Mbarek, Ismail, Said I., Anurag, Verma, Goldstein, David B., Krzysztof, Kiryluk, Renieri, Alessandra, Ferreira, Manuel A. R., J Brent Richards, Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack A, Cirulli, Elizabeth T, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyun, Stockwell, Amy D, Sloofman, Laura G, Jordan, Daniel M, Thompson, Ryan C, Del Valle, Diane, Simons, Nicole, Cheng, Esther, Sebra, Robert, Schadt, Eric E, Kim-Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Buxbaum, Joseph D, Beckmann, Noam D, Charney, Alexander W, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess D, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, J Kenneth, Stuckey, Alex, Salas, Antonio, Bello, Xabier, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Rivero-Calle, Irene, Martinón-Torres, Federico, Ganna, Andrea, Karczewski, Konrad J, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert Jm, Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly M, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicola, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour S, Arabi, Yaseen M, Alqahtani, Saleh A, Al Harthi, Fawz S, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal A, El Bardisy, Hadeel, Fawzy, Mohammad, Cai, Fang, Soranzo, Nicole, Butterworth, Adam, Geschwind, Daniel H, Arteaga, Stephanie, Stephens, Alexi, Butte, Manish J, Boutros, Paul C, Yamaguchi, Takafumi N, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul J, Broudy, Michael E, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yve, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Tokunaga, Katsushi, Sugiyama, Masaya, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak S, Zeberg, Hugo, Grzymski, Joseph J, Washington, Nicole L, Ossowski, Stephan, Ludwig, Kerstin U, Schulte, Eva C, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said I, Verma, Anurag, Goldstein, David B, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel A R, Richards, J Brent, Data Science Genetic Epidemiology Lab, Institute for Molecular Medicine Finland, University of Helsinki, and Helsinki Institute of Life Science HiLIFE

Subjects
Infectious Medicine, Cancer Research, Host genetics is a key determinant of COVID-19 outcomes. Previously, Infektionsmedicin, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights, Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, Genetics, Humans, Exome, Genetic Predisposition to Disease, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Medicinsk genetik, SARS-CoV-2, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, 1184 Genetics, developmental biology, physiology, COVID-19, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5, 737 controls, Toll-Like Receptor 7, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, 085 severe disease cases and 571, thereby informing therapeutics development. Here, Medical Genetics, Genome-Wide Association Study
Abstract

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

Published
2022

13. Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Author

Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack A, Cirulli, Elizabeth T, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyun, Stockwell, Amy D, Sloofman, Laura G, Jordan, Daniel M, Thompson, Ryan C, Del Valle, Diane, Simons, Nicole, Cheng, Esther, Sebra, Robert, Schadt, Eric E, Kim-Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Buxbaum, Joseph D, Beckmann, Noam D, Charney, Alexander W, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess D, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, J Kenneth, Stuckey, Alex, Salas, Antonio, Bello, Xabier, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Rivero-Calle, Irene, Martinón-Torres, Federico, Ganna, Andrea, Karczewski, Konrad J, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert Jm, Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklós, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly M, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicolas, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour S, Arabi, Yaseen M, Alqahtani, Saleh A, Al Harthi, Fawz S, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal A, El Bardisy, Hadeel, Fawzy, Mohammad, Cai, Fang, Soranzo, Nicole, Butterworth, Adam, Geschwind, Daniel H, Arteaga, Stephanie, Stephens, Alexis, Butte, Manish J, Boutros, Paul C, Yamaguchi, Takafumi N, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul J, Broudy, Michael E, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yves, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Tokunaga, Katsushi, Sugiyama, Masaya, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak S, Zeberg, Hugo, Grzymski, Joseph J, Washington, Nicole L, Ossowski, Stephan, Ludwig, Kerstin U, Schulte, Eva C, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said I, Verma, Anurag, Goldstein, David B, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel A R, Richards, J Brent, Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack A, Cirulli, Elizabeth T, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyun, Stockwell, Amy D, Sloofman, Laura G, Jordan, Daniel M, Thompson, Ryan C, Del Valle, Diane, Simons, Nicole, Cheng, Esther, Sebra, Robert, Schadt, Eric E, Kim-Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Buxbaum, Joseph D, Beckmann, Noam D, Charney, Alexander W, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess D, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, J Kenneth, Stuckey, Alex, Salas, Antonio, Bello, Xabier, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Rivero-Calle, Irene, Martinón-Torres, Federico, Ganna, Andrea, Karczewski, Konrad J, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert Jm, Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklós, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly M, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicolas, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour S, Arabi, Yaseen M, Alqahtani, Saleh A, Al Harthi, Fawz S, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal A, El Bardisy, Hadeel, Fawzy, Mohammad, Cai, Fang, Soranzo, Nicole, Butterworth, Adam, Geschwind, Daniel H, Arteaga, Stephanie, Stephens, Alexis, Butte, Manish J, Boutros, Paul C, Yamaguchi, Takafumi N, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul J, Broudy, Michael E, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yves, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Tokunaga, Katsushi, Sugiyama, Masaya, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak S, Zeberg, Hugo, Grzymski, Joseph J, Washington, Nicole L, Ossowski, Stephan, Ludwig, Kerstin U, Schulte, Eva C, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said I, Verma, Anurag, Goldstein, David B, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel A R, and Richards, J Brent

Abstract

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

Published
2022
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14. Unlocking capacities of viral genomics for the COVID-19 pandemic response

Author

Knyazev, Sergey, Chhugani, Karishma, Sarwal, Varuni, Ayyala, Ram, Singh, Harman, Karthikeyan, Smruthi, Deshpande, Dhrithi, Comarova, Zoia, Lu, Angela, Porozov, Yuri, Wu, Aiping, Abedalthagafi, Malak S., Nagaraj, Shivashankar H., Smith, Adam L., Skums, Pavel, Ladner, Jason, Tsan-Yuk Lam, Tommy, Wu, Nicholas C., Zelikovsky, Alex, Knight, Rob, Crandall, Keith A., and Mangul, Serghei

Subjects
Genomics (q-bio.GN), FOS: Biological sciences, Populations and Evolution (q-bio.PE), Quantitative Biology - Genomics, Quantitative Biology - Populations and Evolution, Article
Abstract

More than any other infectious disease epidemic, the COVID-19 pandemic has been characterized by the generation of large volumes of viral genomic data at an incredible pace due to recent advances in high-throughput sequencing technologies, the rapid global spread of SARS-CoV-2, and its persistent threat to public health. However, distinguishing the most epidemiologically relevant information encoded in these vast amounts of data requires substantial effort across the research and public health communities. Studies of SARS-CoV-2 genomes have been critical in tracking the spread of variants and understanding its epidemic dynamics, and may prove crucial for controlling future epidemics and alleviating significant public health burdens. Together, genomic data and bioinformatics methods enable broad-scale investigations of the spread of SARS-CoV-2 at the local, national, and global scales and allow researchers the ability to efficiently track the emergence of novel variants, reconstruct epidemic dynamics, and provide important insights into drug and vaccine development and disease control. Here, we discuss the tremendous opportunities that genomics offers to unlock the effective use of SARS-CoV-2 genomic data for efficient public health surveillance and guiding timely responses to COVID-19.

Published
2021

15. Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

Author

Povysil, Gundula, primary, Butler-Laporte, Guillaume, additional, Shang, Ning, additional, Wang, Chen, additional, Khan, Atlas, additional, Alaamery, Manal, additional, Nakanishi, Tomoko, additional, Zhou, Sirui, additional, Forgetta, Vincenzo, additional, Eveleigh, Robert J.M., additional, Bourgey, Mathieu, additional, Aziz, Naveed, additional, Jones, Steven J.M., additional, Knoppers, Bartha, additional, Scherer, Stephen W., additional, Strug, Lisa J., additional, Lepage, Pierre, additional, Ragoussis, Jiannis, additional, Bourque, Guillaume, additional, Alghamdi, Jahad, additional, Aljawini, Nora, additional, Albes, Nour, additional, Al-Afghani, Hani M., additional, Alghamdi, Bader, additional, Almutairi, Mansour S., additional, Mahmoud, Ebrahim Sabri, additional, Abu-Safieh, Leen, additional, El Bardisy, Hadeel, additional, Harthi, Fawz S. Al, additional, Alshareef, Abdulraheem, additional, Suliman, Bandar Ali, additional, Alqahtani, Saleh A., additional, Almalik, Abdulaziz, additional, Alrashed, May M., additional, Massadeh, Salam, additional, Mooser, Vincent, additional, Lathrop, Mark, additional, Fawzy, Mohamed, additional, Arabi, Yaseen M., additional, Mbarek, Hamdi, additional, Saad, Chadi, additional, Al-Muftah, Wadha, additional, Jung, Junghyun, additional, Mangul, Serghei, additional, Badji, Radja, additional, Thani, Asma Al, additional, Ismail, Said I., additional, Gharavi, Ali G., additional, Abedalthagafi, Malak S., additional, Richards, J. Brent, additional, Goldstein, David B., additional, and Kiryluk, Krzysztof, additional

Published
2021
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16. Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5

Author

Abedalthagafi, Malak S., primary, Merrill, Parker H., additional, Bi, Wenya Linda, additional, Jones, Robert T., additional, Listewnik, Marc L., additional, Ramkissoon, Shakti H., additional, Thorner, Aaron R., additional, Dunn, Ian F., additional, Beroukhim, Rameen, additional, Alexander, Brian M., additional, Brastianos, Priscilla K., additional, Francis, Joshua M., additional, Folkerth, Rebecca D., additional, Ligon, Keith L., additional, Hummelen, Paul Van, additional, Ligon, Azra H., additional, and Santagata, Sandro, additional

Published
2014
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17. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

Author

Shankar, Ganesh Mani, Taylor-Weiner, Amaro, Lelic, Nina, Jones, Robert T, Kim, James C, Francis, Joshua M, Abedalthagafi, Malak S, Borges, Lawrence Francis, Coumans, Jean-Valery C E, Curry, William Thomas, Nahed, Brian Vala, Shin, John H, Paek, Sun Ha, Park, Sung-Hye, Stewart, Chip, Lawrence, Michael S, Cibulskis, Kristian, Thorner, Aaron R, Van Hummelen, Paul, Stemmer-Rachamimov, Anat, Batchelor, Tracy Todd, Carter, Scott Lambert, Hoang, Mai P, Santagata, Sandro, Louis, David N., Barker, Frederick George, Meyerson, Matthew Langer, Getz, Gad A, Brastianos, Priscilla Kalliope, and Cahill, Daniel P.

Subjects
central nervous system, hemangioblastoma, deep sequencing, somatic gene alterations, Von Hippel-Lindau gene, hypoxia-inducible signaling
Abstract

Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.

Published
2014
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18. Analytical code sharing practices in biomedical research.

Author

Sharma NK, Ayyala R, Deshpande D, Patel YM, Munteanu V, Ciorba D, Fiscutean A, Vahed M, Sarkar A, Guo R, Moore A, Darci-Maher N, Nogoy NA, Abedalthagafi MS, and Mangul S

Abstract

Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, affects transparency and reproducibility of studies, which are critical to the advancement of science. Many published studies are not reproducible due to insufficient documentation, code, and data being shared. We conducted a comprehensive analysis of 453 manuscripts published between 2016-2021 and found that 50.1% of them fail to share the analytical code. Even among those that did disclose their code, a vast majority failed to offer additional research outputs, such as data. Furthermore, only one in ten papers organized their code in a structured and reproducible manner. We discovered a significant association between the presence of code availability statements and increased code availability (p=2.71×10 -9 ). Additionally, a greater proportion of studies conducting secondary analyses were inclined to share their code compared to those conducting primary analyses (p=1.15*10 -07 ). In light of our findings, we propose raising awareness of code sharing practices and taking immediate steps to enhance code availability to improve reproducibility in biomedical research. By increasing transparency and reproducibility, we can promote scientific rigor, encourage collaboration, and accelerate scientific discoveries. We must prioritize open science practices, including sharing code, data, and other research products, to ensure that biomedical research can be replicated and built upon by others in the scientific community.

Published
2023
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19. Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.

Author

Butler-Laporte G, Povysil G, Kosmicki JA, Cirulli ET, Drivas T, Furini S, Saad C, Schmidt A, Olszewski P, Korotko U, Quinodoz M, Çelik E, Kundu K, Walter K, Jung J, Stockwell AD, Sloofman LG, Jordan DM, Thompson RC, Del Valle D, Simons N, Cheng E, Sebra R, Schadt EE, Kim-Schulze S, Gnjatic S, Merad M, Buxbaum JD, Beckmann ND, Charney AW, Przychodzen B, Chang T, Pottinger TD, Shang N, Brand F, Fava F, Mari F, Chwialkowska K, Niemira M, Pula S, Baillie JK, Stuckey A, Salas A, Bello X, Pardo-Seco J, Gómez-Carballa A, Rivero-Calle I, Martinón-Torres F, Ganna A, Karczewski KJ, Veerapen K, Bourgey M, Bourque G, Eveleigh RJ, Forgetta V, Morrison D, Langlais D, Lathrop M, Mooser V, Nakanishi T, Frithiof R, Hultström M, Lipcsey M, Marincevic-Zuniga Y, Nordlund J, Schiabor Barrett KM, Lee W, Bolze A, White S, Riffle S, Tanudjaja F, Sandoval E, Neveux I, Dabe S, Casadei N, Motameny S, Alaamery M, Massadeh S, Aljawini N, Almutairi MS, Arabi YM, Alqahtani SA, Al Harthi FS, Almutairi A, Alqubaishi F, Alotaibi S, Binowayn A, Alsolm EA, El Bardisy H, Fawzy M, Cai F, Soranzo N, Butterworth A, Geschwind DH, Arteaga S, Stephens A, Butte MJ, Boutros PC, Yamaguchi TN, Tao S, Eng S, Sanders T, Tung PJ, Broudy ME, Pan Y, Gonzalez A, Chavan N, Johnson R, Pasaniuc B, Yaspan B, Smieszek S, Rivolta C, Bibert S, Bochud PY, Dabrowski M, Zawadzki P, Sypniewski M, Kaja E, Chariyavilaskul P, Nilaratanakul V, Hirankarn N, Shotelersuk V, Pongpanich M, Phokaew C, Chetruengchai W, Tokunaga K, Sugiyama M, Kawai Y, Hasegawa T, Naito T, Namkoong H, Edahiro R, Kimura A, Ogawa S, Kanai T, Fukunaga K, Okada Y, Imoto S, Miyano S, Mangul S, Abedalthagafi MS, Zeberg H, Grzymski JJ, Washington NL, Ossowski S, Ludwig KU, Schulte EC, Riess O, Moniuszko M, Kwasniewski M, Mbarek H, Ismail SI, Verma A, Goldstein DB, Kiryluk K, Renieri A, Ferreira MAR, and Richards JB

Subjects
Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Toll-Like Receptor 7 genetics, SARS-CoV-2 genetics, Exome genetics, COVID-19 genetics
Abstract

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Biobanque Québécoise de la Covid-19: Brent Richards’s institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline and Biogen for projects unrelated to this research. He is the CEO of 5 Prime Sciences Inc (www.5primesciences.com). DeCOI: Oliver Witzke has received research grants for clinical studies, speaker’s fees, honoraria and travel expenses from Amgen, Alexion, Astellas, Basilea, Biotest, Bristol-Myers Squibb, Correvio, Chiesi, Gilead, Hexal, Janssen, Dr. F. Köhler Chemie, MSD, Novartis, Roche, Pfizer, Sanofi, Takeda, TEVA and UCB. Kerstin U. Ludwig is co-founder and holds equity in the LAMPseq Diagnostics GmbH. UP serves as ad hoc advisor for Sanofi-Pasteur, BioNtech and Sobi and is member of the SAB of Leukocare. Christoph D. Spinner reports grants, personal fees from AstraZeneca, personal fees and non-financial support from BBraun Melsungen, grants, personal fees and non-financial support from Gilead Sciences, grants and personal fees from Janssen-Cilag, personal fees from Eli Lilly, personal fees from Formycon, personal fees from Roche, other from Apeiron, grants and personal fees from MSD, grants from Cepheid, personal fees from GSK, personal fees from Molecular partners, other from Eli Lilly, personal fees from SOBI during the conduct of the study; personal fees from AbbVie, personal fees from MSD, grants and personal fees from ViiV Healthcare, outside the submitted work. Jochen Schneider received grants and/or personal fees from Gilead Sciences, Janssen-Cilag, and from AbbVie outside the submitted work. Philipp Koehler reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, medupdate GmbH, MedMedia, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office; Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. Oliver A. Cornely reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI, Shionogi; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley. Genentech: Amy D Stockwell, Fang Cai, and Brian L Yaspan are, or were at the execution of the study, full time employees of Genentech with stock and stock options in Roche. Helix Exome+ and Healthy Nevada Project COVID-19 Phenotypes: Alexandre Bolze, Kelly M Schiabor Barrett, Simon White, Nicole L Washington, Francisco Tanudjaja, Stephen Riffle, Efren Sandoval, and Elizabeth T Cirulli are employees of Helix. Regeneron: Jack A Kosmicki and Manuel AR Ferreira are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals. Vanda CALYPSO COVID-19: Bartlomiej Przychodzen and Sandra Smieszek are employees of Vanda Pharmaceuticals Inc.

Published
2022
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