CAVACHON: a hierarchical variational autoencoder to integrate multi-modal single-cell data

arXiv (Cornell University)

Abstract

Paired single-cell sequencing technologies enable the simultaneous measurement of complementary modalities of molecular data at single-cell resolution. Along with the advances in these technologies, many methods based on variational autoencoders have been developed to integrate these data. However, these methods do not explicitly incorporate prior biological relationships between the data modalities, which could significantly enhance modeling and interpretation. We propose a novel probabilistic learning framework that explicitly incorporates conditional independence relationships between multi-modal data as a directed acyclic graph using a generalized hierarchical variational autoencoder. We demonstrate the versatility of our framework across various applications pertinent to single-cell multi-omics data integration. These include the isolation of common and distinct information from different modalities, modality-specific differential analysis, and integrated cell clustering. We anticipate that the proposed framework can facilitate the construction of highly flexible graphical models that can capture the complexities of biological hypotheses and unravel the connections between different biological data types, such as different modalities of paired single-cell multi-omics data. The implementation of the proposed framework can be found in the repository https://github.com/kuijjerlab/CAVACHON.

Authors 9

1. Ping‐Han Hsieh
   Affiliation as printed

   Centre for Molecular Medicine Norway (NCMM) , Nordic EMBL Partnership , University of Oslo , Oslo , Norway;

2. Ru-Xiu Hsiao

   National Taiwan University

   Affiliation as printed

   Genome and Systems Biology Degree Program , National Taiwan University , Taipei , Taiwan;

3. Katalin Ferenc

   University of Oslo

   Affiliation as printed

   Centre for Molecular Medicine Norway (NCMM) , Nordic EMBL Partnership , University of Oslo , Oslo , Norway;

   Department of Informatics , University of Oslo , Oslo Norway ;

4. Anthony Mathelier

   University of Oslo

   Affiliation as printed

   Center for Bioinformatics , University of Oslo , Oslo , Norway;

   Centre for Molecular Medicine Norway (NCMM) , Nordic EMBL Partnership , University of Oslo , Oslo , Norway ;

5. Rebekka Burkholz

   Helmholtz Center for Information Security

   Affiliation as printed

   CISPA Helmholtz Center for Information Security , Saarland , Germany;

6. Chien‐Yu Chen
7. Geir Kjetil Sandve

   University of Oslo

   Affiliation as printed

   Department of Informatics , University of Oslo , Oslo , Norway

8. Tatiana Belova
   Affiliation as printed

   Centre for Molecular Medicine Norway (NCMM) , Nordic EMBL Partnership , University of Oslo , Oslo , Norway;

9. Marieke L. Kuijjer Aachen Department of Pathology, Leiden University Medical Center

   University of Oslo · Leiden University Medical Center

   Affiliation as printed

   Centre for Molecular Medicine Norway (NCMM) , Nordic EMBL Partnership , University of Oslo , Oslo , Norway ;

   Department of Pathology Leiden University Medical Center ;