Inferring cellular heterogeneity of associations from single cell genomics

Bioinformatics
Maya LevyIrit Gat-Viks

Abstract

Cell-to-cell variation has uncovered associations between cellular phenotypes. However, it remains challenging to address the cellular diversity of such associations. Here we do not rely on the conventional assumption that the same association holds throughout the entire cell population. Instead, we assume that associations may exist in a certain subset of the cells. We developed CENA to reliably predict pairwise associations together with the cell subsets in which the associations are detected. CENA does not rely on predefined subsets but only requires that the cells of each predicted subset would share a certain characteristic state. CENA may therefore reveal dynamic modulation of dependencies along cellular trajectories of temporally evolving states. Using simulated data, we show the advantage of CENA over existing methods and its scalability to a large number of cells. Application of CENA to real biological data demonstrates dynamic changes in associations that would be otherwise masked. CENA is available as an R package at Github: https://github.com/mayalevy/CENA, and is accompanied by a complete set of documentations and instructions. Supplementary data are available at Bioinformatics online.

References

Sep 5, 2007·Biochemical and Biophysical Research Communications·Rikinori MurayamaTorahiko Tanaka
Nov 9, 2016·Nature Biotechnology·Allon WagnerNir Yosef
Jul 18, 2017·Molecular Aspects of Medicine·Tallulah S Andrews, Martin Hemberg
Jun 11, 2018·Cell Systems·Yael SteuermanIrit Gat-Viks
Jan 9, 2019·Nature Reviews. Genetics·Vladimir Yu KiselevMartin Hemberg
Mar 20, 2019·Nature Methods·Amit FrishbergIrit Gat-Viks
Mar 28, 2019·Scientific Reports·V A TraagN J van Eck
Apr 3, 2019·Nature Biotechnology·Wouter SaelensYvan Saeys
Apr 10, 2019·Nature Methods·Michael A SkinniderLeonard J Foster
Jun 5, 2019·Genome Biology·Giovanni IaconoHolger Heyn
Jul 17, 2019·Nature Methods·Nikolas BarkasPeter V Kharchenko
Sep 29, 2019·Nature Communications·David DeTomasoNir Yosef

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