mcBERT: Patient-Level Single-cell Transcriptomics Data Representation

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Single-cell RNA sequencing (scRNA-seq) transcriptomics improves our understanding of cellular heterogeneity in healthy and pathological states. However, most scRNA-seq analyses remain confined to single cells or distinct cell populations, limiting their clinical applicability. Addressing the need to translate single-cell insights into a patient-level disease understanding, we introduce mcBERT, a new method that leverages scRNA-seq data and a transformer-based model to generate integrative patient representations using a self-supervised learning phase followed by contrastive learning to refine these representations. Our evaluations of mcBERT across 7 million cells from 1223 individuals encompassing diverse disease states in heart, kidney, blood cell, and lung tissues show that learned representations facilitate a robust identification of disease cohorts and enable comparisons of patient similarity. Moreover, our findings indicate that mcBERT can accurately classify disease phenotypes, also in previously unseen biospecimens and patients. Independent of the specific tissue, mcBERT extends the utility of scRNA-seq data from cellular analysis to potentially actionable patient-centric applications.

Authors 7

1. Benedikt von Querfurth Aachen Communication and Distributed Systems

   RWTH Aachen University

   Affiliation as printed

   Communication and Distributed Systems, RWTH Aachen University, Ahornstraße 55, Aachen, 52074, NRW, Germany

   Communication and Distributed Systems, RWTH Aachen University, Germany;

   Communication and Distributed Systems, RWTH Aachen University, Germany

2. Johannes Lohmöller corresponding Aachen Communication and Distributed Systems

   RWTH Aachen University

   Affiliation as printed

   Communication and Distributed Systems, RWTH Aachen University, Ahornstraße 55, Aachen, 52074, NRW, Germany

   Communication and Distributed Systems, RWTH Aachen University, Germany

3. Jan Pennekamp corresponding Aachen Clinic for Gastroenterology Metabolic Disorders and Internal Intensive Medicine (Medical Clinic III) Communication and Distributed Systems

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Gastroenterology, Metabolic Disorders and Internal Intensive Medicine (Medical Clinic III), University Hospital RWTH Aachen, Pauwelsstraße 30, Aachen, 52074, NRW, Germany

   Communication and Distributed Systems, RWTH Aachen University, Ahornstraße 55, Aachen, 52074, NRW, Germany

   Communication and Distributed Systems, RWTH Aachen University, Germany;

   Communication and Distributed Systems, RWTH Aachen University, Germany

4. Tore Bleckwehl Aachen Clinic for Renal and Hypertensive Disorders Rheumatological and Immunological Diseases (Medical Clinic II) Department of Medicine II

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), University Hospital RWTH Aachen, Pauwelsstraße 30, Aachen, 52074, NRW, Germany

   Department of Medicine II, Uniklinik Aachen, Germany

5. Rafael Kramann Aachen Clinic for Renal and Hypertensive Disorders Rheumatological and Immunological Diseases (Medical Clinic II) Department of Medicine II Communication and Distributed Systems

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), University Hospital RWTH Aachen, Pauwelsstraße 30, Aachen, 52074, NRW, Germany

   Department of Medicine II, Uniklinik Aachen, Germany

   Communication and Distributed Systems, RWTH Aachen University, Germany

6. Klaus Wehrle Aachen Communication and Distributed Systems Department of Medicine II

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Communication and Distributed Systems, RWTH Aachen University, Ahornstraße 55, Aachen, 52074, NRW, Germany

   Communication and Distributed Systems, RWTH Aachen University, Germany;

   Department of Medicine II, Uniklinik Aachen, Germany

7. Sikander Hayat corresponding Aachen Clinic for Renal and Hypertensive Disorders Rheumatological and Immunological Diseases (Medical Clinic II) Department of Medicine II

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), University Hospital RWTH Aachen, Pauwelsstraße 30, Aachen, 52074, NRW, Germany

   Department of Medicine II, Uniklinik Aachen, Germany