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1. The chromatin landscape of healthy and injured cell types in the human kidney

Author

Debora L. Gisch, Michelle Brennan, Blue B. Lake, Jeannine Basta, Mark S. Keller, Ricardo Melo Ferreira, Shreeram Akilesh, Reetika Ghag, Charles Lu, Ying-Hua Cheng, Kimberly S. Collins, Samir V. Parikh, Brad H. Rovin, Lynn Robbins, Lisa Stout, Kimberly Y. Conklin, Dinh Diep, Bo Zhang, Amanda Knoten, Daria Barwinska, Mahla Asghari, Angela R. Sabo, Michael J. Ferkowicz, Timothy A. Sutton, Katherine J. Kelly, Ian H. De Boer, Sylvia E. Rosas, Krzysztof Kiryluk, Jeffrey B. Hodgin, Fadhl Alakwaa, Seth Winfree, Nichole Jefferson, Aydın Türkmen, Joseph P. Gaut, Nils Gehlenborg, Carrie L. Phillips, Tarek M. El-Achkar, Pierre C. Dagher, Takashi Hato, Kun Zhang, Jonathan Himmelfarb, Matthias Kretzler, Shamim Mollah, the Kidney Precision Medicine Project (KPMP), Sanjay Jain, Michael Rauchman, and Michael T. Eadon

Subjects
Science
Abstract

Abstract There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney’s active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

Published
2024
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2. Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in context

Author

Francesca Sperotto, Alba Gutiérrez-Sacristán, Simran Makwana, Xiudi Li, Valerie N. Rofeberg, Tianxi Cai, Florence T. Bourgeois, Gilbert S. Omenn, David A. Hanauer, Carlos Sáez, Clara-Lea Bonzel, Emily Bucholz, Audrey Dionne, Matthew D. Elias, Noelia García-Barrio, Tomás González González, Richard W. Issitt, Kate F. Kernan, Jessica Laird-Gion, Sarah E. Maidlow, Kenneth D. Mandl, Taha Mohseni Ahooyi, Cinta Moraleda, Michele Morris, Karyn L. Moshal, Miguel Pedrera-Jiménez, Mohsin A. Shah, Andrew M. South, Anastasia Spiridou, Deanne M. Taylor, Guillaume Verdy, Shyam Visweswaran, Xuan Wang, Zongqi Xia, Joany M. Zachariasse, Jane W. Newburger, Paul Avillach, James R. Aaron, Atif Adam, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li LLJ. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, Rafael Badenes, James Balshi, Ashley Batugo, Brendin R. Beaulieu-Jones, Brett K. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Riccardo Bellazzi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Arianna Dagliati, Mohamad Daniar, Christel Daniel, Priyam Das, Batsal Devkota, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Rachel SJ. Goh, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Yuk-Lam Ho, John H. Holmes, Jacqueline P. Honerlaw, Chuan Hong, Kenneth M. Huling, Meghan R. Hutch, Anne Sophie Jannot, Vianney Jouhet, Mundeep K. Kainth, Kernan F. Kate, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Daniel A. Key, Katie Kirchoff, Jeffrey G. Klann, Isaac S. Kohane, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Qi Long, Sara Lozano-Zahonero, Yuan Luo, Kristine E. Lynch, Sadiqa Mahmood, Adeline Makoudjou, Alberto Malovini, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Bertrand Moal, Jason H. Moore, Jeffrey S. Morris, Sajad Mousavi, Danielle L. Mowery, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Antoine Neuraz, Jane Newburger, Kee Yuan Ngiam, Wanjiku FM. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Lav P. Patel, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Nekane Romero-Garcia, Paula Rubio-Mayo, Paolo Sacchi, Elisa Salamanca, Malarkodi Jebathilagam Samayamuthu, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Emily R. Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Zachary H. Strasser, Amelia LM. Tan, Bryce W.Q. Tan, Byorn W.L. Tan, Suzana E. Tanni, Ana I. Terriza-Torres, Valentina Tibollo, Patric Tippmann, Emma MS. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Demian Wassermann, Griffin M. Weber, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Janet J. Zahner, Alberto Zambelli, Harrison G. Zhang, Daniela Zöller, Valentina Zuccaro, and Chiara Zucco

Subjects
Multisystem inflammatory syndrome, Paediatric inflammatory multisystem syndrome, COVID-19, SARS-CoV-2, Variants, Pediatrics, Medicine (General), R5-920
Abstract

Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Published
2023
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3. Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort studyResearch in Context

Author

Arianna Dagliati, Zachary H. Strasser, Zahra Shakeri Hossein Abad, Jeffrey G. Klann, Kavishwar B. Wagholikar, Rebecca Mesa, Shyam Visweswaran, Michele Morris, Yuan Luo, Darren W. Henderson, Malarkodi Jebathilagam Samayamuthu, Bryce W.Q. Tan, Guillame Verdy, Gilbert S. Omenn, Zongqi Xia, Riccardo Bellazzi, Shawn N. Murphy, John H. Holmes, Hossein Estiri, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Paul Avillach, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Clara-Lea Bonzel, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Tianxi Cai, Mario Cannataro, Aldo Carmona, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Priyam Das, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García- Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Alba Gutiérrez-Sacristán, Larry Han, David A. Hanauer, Christian Haverkamp, Derek Y. Hazard, Bing He, Martin Hilka, Yuk-Lam Ho, Chuan Hong, Kenneth M. Huling, Meghan R. Hutch, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Daniel A. Key, Katie Kirchoff, Isaac S. Kohane, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Sarah E. Maidlow, Adeline Makoudjou, Alberto Malovini, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Bertrand Moal, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Danielle L. Mowery, Douglas A. Murad, Thomas P. Naughton, Carlos Tadeu Breda Neto, Antoine Neuraz, Jane Newburger, Kee Yuan Ngiam, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Lav P. Patel, Miguel Pedrera-Jiménez, Emily R. Pfaff, Ashley C. Pfaff, Danielle Pillion, Sara Pizzimenti, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Emily R. Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Andrew M. South, Anastasia Spiridou, Amelia L.M. Tan, Byorn W.L. Tan, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Valentina Tibollo, Patric Tippmann, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Yi-Ju Tseng, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Guillaume Verdy, Jill-Jênn Vie, Michele Vitacca, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Griffin M. Weber, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Alberto Zambelli, Harrison G. Zhang, Daniela Zo¨ller, Valentina Zuccaro, and Chiara Zucco

Subjects
Post-acute sequelae of SARS-CoV-2, PASC, COVID-19, SARS-CoV-2, Electronic health records, Medicine (General), R5-920
Abstract

Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.

Published
2023
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4. International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality

Author

Griffin M. Weber, Chuan Hong, Zongqi Xia, Nathan P. Palmer, Paul Avillach, Sehi L’Yi, Mark S. Keller, Shawn N. Murphy, Alba Gutiérrez-Sacristán, Clara-Lea Bonzel, Arnaud Serret-Larmande, Antoine Neuraz, Gilbert S. Omenn, Shyam Visweswaran, Jeffrey G. Klann, Andrew M. South, Ne Hooi Will Loh, Mario Cannataro, Brett K. Beaulieu-Jones, Riccardo Bellazzi, Giuseppe Agapito, Mario Alessiani, Bruce J. Aronow, Douglas S. Bell, Vincent Benoit, Florence T. Bourgeois, Luca Chiovato, Kelly Cho, Arianna Dagliati, Scott L. DuVall, Noelia García Barrio, David A. Hanauer, Yuk-Lam Ho, John H. Holmes, Richard W. Issitt, Molei Liu, Yuan Luo, Kristine E. Lynch, Sarah E. Maidlow, Alberto Malovini, Kenneth D. Mandl, Chengsheng Mao, Michael E. Matheny, Jason H. Moore, Jeffrey S. Morris, Michele Morris, Danielle L. Mowery, Kee Yuan Ngiam, Lav P. Patel, Miguel Pedrera-Jimenez, Rachel B. Ramoni, Emily R. Schriver, Petra Schubert, Pablo Serrano Balazote, Anastasia Spiridou, Amelia L. M. Tan, Byorn W. L. Tan, Valentina Tibollo, Carlo Torti, Enrico M. Trecarichi, Xuan Wang, The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Isaac S. Kohane, Tianxi Cai, and Gabriel A. Brat

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach.

Published
2022
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5. Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort studyResearch in context

Author

Byorn W.L. Tan, Bryce W.Q. Tan, Amelia L.M. Tan, Emily R. Schriver, Alba Gutiérrez-Sacristán, Priyam Das, William Yuan, Meghan R. Hutch, Noelia García Barrio, Miguel Pedrera Jimenez, Noor Abu-el-rub, Michele Morris, Bertrand Moal, Guillaume Verdy, Kelly Cho, Yuk-Lam Ho, Lav P. Patel, Arianna Dagliati, Antoine Neuraz, Jeffrey G. Klann, Andrew M. South, Shyam Visweswaran, David A. Hanauer, Sarah E. Maidlow, Mei Liu, Danielle L. Mowery, Ashley Batugo, Adeline Makoudjou, Patric Tippmann, Daniela Zöller, Gabriel A. Brat, Yuan Luo, Paul Avillach, Riccardo Bellazzi, Luca Chiovato, Alberto Malovini, Valentina Tibollo, Malarkodi Jebathilagam Samayamuthu, Pablo Serrano Balazote, Zongqi Xia, Ne Hooi Will Loh, Lorenzo Chiudinelli, Clara-Lea Bonzel, Chuan Hong, Harrison G. Zhang, Griffin M. Weber, Isaac S. Kohane, Tianxi Cai, Gilbert S. Omenn, John H. Holmes, Kee Yuan Ngiam, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Brendin R. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García-Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tomás González González, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Jacqueline P. Honerlaw, Kenneth M. Huling, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Kate F. Kernan, Daniel A. Key, Katie Kirchoff, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Simran Makwana, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Jane Newburger, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Miguel Pedrera-Jiménez, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Francesca Sperotto, Anastasia Spiridou, Zachary H. Strasser, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, Joany M. Zachariasse, Janet J. Zahner, Alberto Zambelli, Valentina Zuccaro, and Chiara Zucco

Subjects
COVID-19, Acute kidney injury, SARS-CoV-2, Chronic kidney disease, Electronic health records, Medicine (General), R5-920
Abstract

Summary: Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p

Published
2023
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6. International electronic health record-derived COVID-19 clinical course profiles: the 4CE consortium

Author

Gabriel A. Brat, Griffin M. Weber, Nils Gehlenborg, Paul Avillach, Nathan P. Palmer, Luca Chiovato, James Cimino, Lemuel R. Waitman, Gilbert S. Omenn, Alberto Malovini, Jason H. Moore, Brett K. Beaulieu-Jones, Valentina Tibollo, Shawn N. Murphy, Sehi L’ Yi, Mark S. Keller, Riccardo Bellazzi, David A. Hanauer, Arnaud Serret-Larmande, Alba Gutierrez-Sacristan, John J. Holmes, Douglas S. Bell, Kenneth D. Mandl, Robert W. Follett, Jeffrey G. Klann, Douglas A. Murad, Luigia Scudeller, Mauro Bucalo, Katie Kirchoff, Jean Craig, Jihad Obeid, Vianney Jouhet, Romain Griffier, Sebastien Cossin, Bertrand Moal, Lav P. Patel, Antonio Bellasi, Hans U. Prokosch, Detlef Kraska, Piotr Sliz, Amelia L. M. Tan, Kee Yuan Ngiam, Alberto Zambelli, Danielle L. Mowery, Emily Schiver, Batsal Devkota, Robert L. Bradford, Mohamad Daniar, Christel Daniel, Vincent Benoit, Romain Bey, Nicolas Paris, Patricia Serre, Nina Orlova, Julien Dubiel, Martin Hilka, Anne Sophie Jannot, Stephane Breant, Judith Leblanc, Nicolas Griffon, Anita Burgun, Melodie Bernaux, Arnaud Sandrin, Elisa Salamanca, Sylvie Cormont, Thomas Ganslandt, Tobias Gradinger, Julien Champ, Martin Boeker, Patricia Martel, Loic Esteve, Alexandre Gramfort, Olivier Grisel, Damien Leprovost, Thomas Moreau, Gael Varoquaux, Jill-Jênn Vie, Demian Wassermann, Arthur Mensch, Charlotte Caucheteux, Christian Haverkamp, Guillaume Lemaitre, Silvano Bosari, Ian D. Krantz, Andrew South, Tianxi Cai, and Isaac S. Kohane

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries ( www.covidclinical.net ). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

Published
2020
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9. SurvMaximin: Robust federated approach to transporting survival risk prediction models.

Author

Xuan Wang, Harrison G. Zhang, Xin Xiong, Chuan Hong, Griffin M. Weber, Gabriel A. Brat, Clara-Lea Bonzel, Yuan Luo 0001, Rui Duan, Nathan P. Palmer, Meghan R. Hutch, Alba Gutiérrez-Sacristán, Riccardo Bellazzi, Luca Chiovato, Kelly Cho, Arianna Dagliati, Hossein Estiri, Noelia García-Barrio, Romain Griffier, David A. Hanauer, Yuk-Lam Ho, John H. Holmes, Mark S. Keller, Jeffrey G. Klann, Sehi L'Yi, Sara Lozano-Zahonero, Sarah E. Maidlow, Adeline Makoudjou, Alberto Malovini, Bertrand Moal, Jason H. Moore, Michele Morris, Danielle L. Mowery, Shawn N. Murphy, Antoine Neuraz, Kee Yuan Ngiam, Gilbert S. Omenn, Lav P. Patel, Miguel Pedrera-Jiménez, Andrea Prunotto, Malarkodi J. Samayamuthu, Fernando J. Sanz Vidorreta, Emily Schriver, Petra Schubert, Pablo Serrano-Balazote, Andrew M. South, Amelia L. M. Tan, Byorn W. L. Tan, Valentina Tibollo, Patric Tippmann, Shyam Visweswaran, Zongqi Xia, William Yuan, Daniela Zöller, Isaac S. Kohane, Paul Avillach, Zijian Guo, and Tianxi Cai

Published
2022
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10. Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

Author

Byorn W.L. Tan, Bryce W.Q. Tan, Amelia L.M. Tan, Emily R. Schriver, Alba Gutiérrez-Sacristán, Priyam Das, William Yuan, Meghan R. Hutch, Noelia García Barrio, Miguel Pedrera Jimenez, Noor Abu-el-rub, Michele Morris, Bertrand Moal, Guillaume Verdy, Kelly Cho, Yuk-Lam Ho, Lav P. Patel, Arianna Dagliati, Antoine Neuraz, Jeffrey G. Klann, Andrew M. South, Shyam Visweswaran, David A. Hanauer, Sarah E. Maidlow, Mei Liu, Danielle L. Mowery, Ashley Batugo, Adeline Makoudjou, Patric Tippmann, Daniela Zöller, Gabriel A. Brat, Yuan Luo, Paul Avillach, Riccardo Bellazzi, Luca Chiovato, Alberto Malovini, Valentina Tibollo, Malarkodi Jebathilagam Samayamuthu, Pablo Serrano Balazote, Zongqi Xia, Ne Hooi Will Loh, Lorenzo Chiudinelli, Clara-Lea Bonzel, Chuan Hong, Harrison G. Zhang, Griffin M. Weber, Isaac S. Kohane, Tianxi Cai, Gilbert S. Omenn, John H. Holmes, Kee Yuan Ngiam, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Brendin R. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García-Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tomás González González, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Jacqueline P. Honerlaw, Kenneth M. Huling, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Kate F. Kernan, Daniel A. Key, Katie Kirchoff, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Simran Makwana, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Jane Newburger, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Miguel Pedrera-Jiménez, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Francesca Sperotto, Anastasia Spiridou, Zachary H. Strasser, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, Joany M. Zachariasse, Janet J. Zahner, Alberto Zambelli, Valentina Zuccaro, and Chiara Zucco

Subjects
General Medicine
Abstract

While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.Advanced age (HR 2.77, 95%CI 2.53-3.04, p 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI.COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery.Authors are supported by various funders, with full details stated in the acknowledgement section.

Published
2022

11. Polyphony: an Interactive Transfer Learning Framework for Single-Cell Data Analysis

Author

Furui Cheng, Mark S Keller, Huamin Qu, Nils Gehlenborg, and Qianwen Wang

Subjects
Signal Processing, Computer Vision and Pattern Recognition, Computer Graphics and Computer-Aided Design, Software
Abstract

Reference-based cell-type annotation can significantly reduce time and effort in single-cell analysis by transferring labels from a previously-annotated dataset to a new dataset. However, label transfer by end-to-end computational methods is challenging due to the entanglement of technical (e.g., from different sequencing batches or techniques) and biological (e.g., from different cellular microenvironments) variation, only the first of which must be removed. To address this issue, we propose Polyphony, an interactive transfer learning (ITL) framework, to complement biologists' knowledge with advanced computational methods. Polyphony is motivated and guided by domain experts' needs for a controllable, interactive, and algorithm-assisted annotation process, identified through our multi-round expert interviews with seven biologists. We introduce anchors, analogous cell populations across datasets, as a paradigm to explain the computational process and collect user feedback for model improvement. A set of visualizations and interactions is provided to empower users to add, delete, or modify anchors, resulting in refined cell type annotations. We demonstrate the effectiveness of this approach through quantitative experiments, two hypothetical use cases, and interviews with two biologists. The results show that our anchor-based ITL method takes advantage of both human and machine intelligence in annotating massive single-cell datasets.

Published
2022

12. Vitessce: a framework for integrative visualization of multi-modal and spatially-resolved single-cell data

Author

Mark S Keller, Ilan Gold, Chuck McCallum, Trevor Manz, Peter V Kharchenko, and Nils Gehlenborg

Abstract

Vitessce is an open-source interactive visualization framework for exploration of multi-modal and spatially-resolved single-cell data, with a modular architecture compatible with transcriptomic, proteomic, genome-mapped, and imaging data types. Its modular, coordinated multiple view implementation facilitates a wide range of visualization tasks to support all common single-cell assays. Vitessce is a client-side web application designed to be integrated with computational analysis tools and data resources and does not require specialized server infrastructure. The software is available at http://vitessce.io.

Published
2021

13. Viv: multiscale visualization of high-resolution multiplexed bioimaging data on the web

Author

Trevor Manz, Ilan Gold, Nathan Heath Patterson, Chuck McCallum, Mark S. Keller, Bruce W. Herr, Katy Börner, Jeffrey M. Spraggins, and Nils Gehlenborg

Subjects
Cell Biology, Molecular Biology, Biochemistry, Article, Biotechnology
Abstract

Recent advances in highly multiplexed imaging have enabled the comprehensive profiling of complex tissues in healthy and diseased states, facilitating the study of fundamental biology and human disease in spatially-resolved contexts at subcellular resolution. However, current computational infrastructure to distribute and visualize these data on the web remains complex to set up and maintain. To address these limitations, we have developed Viv—an open-source image visualization library for high-resolution multiplexed image data that is implemented in JavaScript and builds on modern web technologies. Viv directly renders OME-TIFF and OME-NGFF data formats. Three use cases, including integration into Jupyter Notebooks (https://github.com/hms-dbmi/vizarr), a visual exploration tool, and an image viewer (http://avivator.gehlenborglab.org) demonstrate the capabilities of our proposed approach.

Published
2022

14. Developing better digital health measures of Parkinson's disease using free living data and a crowdsourced data analysis challenge.

Author

Solveig K Sieberts, Henryk Borzymowski, Yuanfang Guan, Yidi Huang, Ayala Matzner, Alex Page, Izhar Bar-Gad, Brett Beaulieu-Jones, Yuval El-Hanani, Jann Goschenhofer, Monica Javidnia, Mark S Keller, Yan-Chak Li, Mohammed Saqib, Greta Smith, Ana Stanescu, Charles S Venuto, Robert Zielinski, BEAT-PD DREAM Challenge Consortium, Arun Jayaraman, Luc J W Evers, Luca Foschini, Alex Mariakakis, Gaurav Pandey, Nicholas Shawen, Phil Synder, and Larsson Omberg

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

One of the promising opportunities of digital health is its potential to lead to more holistic understandings of diseases by interacting with the daily life of patients and through the collection of large amounts of real-world data. Validating and benchmarking indicators of disease severity in the home setting is difficult, however, given the large number of confounders present in the real world and the challenges in collecting ground truth data in the home. Here we leverage two datasets collected from patients with Parkinson's disease, which couples continuous wrist-worn accelerometer data with frequent symptom reports in the home setting, to develop digital biomarkers of symptom severity. Using these data, we performed a public benchmarking challenge in which participants were asked to build measures of severity across 3 symptoms (on/off medication, dyskinesia, and tremor). 42 teams participated and performance was improved over baseline models for each subchallenge. Additional ensemble modeling across submissions further improved performance, and the top models validated in a subset of patients whose symptoms were observed and rated by trained clinicians.

Published
2023
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