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Multiscale PHATE Exploration of SARS-CoV-2 Data Reveals Multimodal Signatures of Disease

51 Pages Posted: 23 Nov 2020 Publication Status: Review Complete

See all articles by Manik Kuchroo

Manik Kuchroo

Yale University - Department of Genetics and Computer Science

Jessie Huang

Yale University - Department of Computer Science

Patrick Wong

Yale University - Department of Immunobiology

Jean-Christophe Grenier

Montreal Heart Institute

Dennis Shung

Yale University - Department of Medicine

Alexander Tong

Yale University - Department of Computer Science

Carolina Lucas

Yale University - Department of Immunobiology

Jon Klein

Yale University - Department of Immunobiology

Daniel Burkhardt

Yale University - Department of Genetics

Scott Gigante

Yale University - Computational Biology

Abhinav Godavarthi

Yale University - Department of Applied Mathematics

Benjamin Goldman-Israelow

Yale University - Department of Immunobiology

Tianyang Mao

Yale University - Department of Immunobiology

Ji Eun Oh

Yale University - Department of Immunobiology

Julio Silva

Yale University - Department of Immunobiology

Takehiro Takahashi

Yale University - Department of Immunobiology

Camila Odio

Yale University - Department of Medicine

Arnau Casanovas-Massana

Yale University - Department of Epidemiology of Microbial Diseases

John Fournier

Yale University - Department of Medicine

Yale IMPACT Team

Shelli Farhadian

Yale University - Department of Medicine

Charles S. Dela Cruz

Yale University - Section of Pulmonary and Critical Care and Sleep Medicine

Albert Ko

Yale School of Public Health - Department of Epidemiology of Microbial Diseases

Francis Perry Wilson

Yale University - Clinical and Translational Research Accelerator

Julie Hussin

Montreal Heart Institute

Guy Wolf

Yale University - Applied Mathematics Program

Akiko Iwasaki

Yale University - Department of Immunobiology

Smita Krishnaswamy

Yale University - Department of Genetics

More...

Abstract

The biomedical community is producing increasingly high dimensional datasets, integrated from hundreds of patient samples, which current computational techniques struggle to explore. Here we present Multiscale PHATE, which learns abstracted biological features from data that can be directly predictive of disease. Our approach creates a tree of data granularities that can be cut at coarse levels for high level summarizations, as well as at fine levels for detailed representations on subsets. We apply Multiscale PHATE to study the immune response to COVID-19 in 54 million cells from 168 hospitalized patients. Our analysis identifies pathogenic cellular populations, CD16-hiCD66b-lo neutrophils and IFNγ+GranzymeB+ Th17 cells, and shows that cellular groupings discovered by Multiscale PHATE are directly predictive of disease outcome. We use Multiscale PHATE-derived features to construct two different manifolds of patients, one from abstracted flow cytometry features and another on patient clinical features, both associating immune subsets and clinical markers with outcome.

Conflict of Interest: Dr. Krishnaswamy is on the scientific advisory board of KovaDx and AI Therapeutics. Dr. Iwasaki a member of the SAB for InProTher. Dr. Iwasaki is a co-founder of RIGImmune. Dr. Wilson is founder of Efference. Dr. Ko is a member of the expert panel of the Reckit Global Hygiene Institute. The remaining authors have no competing interests to declare.

Ethical Approval: This study was approved by Yale Human Research Protection Program Institutional Review Boards (FWA00002571, protocol ID 2000027690). Informed consent was obtained from all enrolled patients and healthcare workers.

Suggested Citation

Kuchroo, Manik and Huang, Jessie and Wong, Patrick and Grenier, Jean-Christophe and Shung, Dennis and Tong, Alexander and Lucas, Carolina and Klein, Jon and Burkhardt, Daniel and Gigante, Scott and Godavarthi, Abhinav and Goldman-Israelow, Benjamin and Mao, Tianyang and Oh, Ji Eun and Silva, Julio and Takahashi, Takehiro and Odio, Camila and Casanovas-Massana, Arnau and Fournier, John and Team, Yale IMPACT and Farhadian, Shelli and Dela Cruz, Charles S. and Ko, Albert and Wilson, Francis Perry and Hussin, Julie and Wolf, Guy and Iwasaki, Akiko and Krishnaswamy, Smita, Multiscale PHATE Exploration of SARS-CoV-2 Data Reveals Multimodal Signatures of Disease. Available at SSRN: https://ssrn.com/abstract=3736103 or http://dx.doi.org/10.2139/ssrn.3736103
This version of the paper has not been formally peer reviewed.

Manik Kuchroo

Yale University - Department of Genetics and Computer Science ( email )

333 Cedar Street
New Haven, CT 06520
United States

Jessie Huang

Yale University - Department of Computer Science

P.O. Box 208285
New Haven, CT
United States

Patrick Wong

Yale University - Department of Immunobiology

300 Cedar Street
New Haven, CT 06520
United States

Jean-Christophe Grenier

Montreal Heart Institute ( email )

Montréal, Québec
Canada

Dennis Shung

Yale University - Department of Medicine ( email )

New Haven, CT
United States

Alexander Tong

Yale University - Department of Computer Science ( email )

P.O. Box 208285
New Haven, CT
United States

Carolina Lucas

Yale University - Department of Immunobiology

300 Cedar Street
New Haven, CT 06520
United States

Jon Klein

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Daniel Burkhardt

Yale University - Department of Genetics ( email )

333 Cedar Street
New Haven, CT 06520
United States

Scott Gigante

Yale University - Computational Biology ( email )

New Haven, CT 06520
United States

Abhinav Godavarthi

Yale University - Department of Applied Mathematics ( email )

New Haven, CT 06520
United States

Benjamin Goldman-Israelow

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Tianyang Mao

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Ji Eun Oh

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Julio Silva

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Takehiro Takahashi

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Camila Odio

Yale University - Department of Medicine ( email )

New Haven, CT
United States

Arnau Casanovas-Massana

Yale University - Department of Epidemiology of Microbial Diseases ( email )

New Haven, CT
United States

John Fournier

Yale University - Department of Medicine ( email )

New Haven, CT
United States

Shelli Farhadian

Yale University - Department of Medicine ( email )

New Haven, CT
United States

Charles S. Dela Cruz

Yale University - Section of Pulmonary and Critical Care and Sleep Medicine

New Haven, CT 06520
United States

Albert Ko

Yale School of Public Health - Department of Epidemiology of Microbial Diseases ( email )

United States

Francis Perry Wilson

Yale University - Clinical and Translational Research Accelerator ( email )

New Haven, CT 06520
United States

Julie Hussin

Montreal Heart Institute ( email )

Montréal, Québec
Canada

Guy Wolf

Yale University - Applied Mathematics Program

51 Prospect Street
New Haven, CT 06511
United States

Akiko Iwasaki

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Smita Krishnaswamy (Contact Author)

Yale University - Department of Genetics ( email )

333 Cedar Street
New Haven, CT 06520
United States

No contact information is available for Yale IMPACT Team

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