Interpretable deep learning in single-cell omics.

Manoj M Wagle, Siqu Long, Carissa Chen, Chunlei Liu, Pengyi Yang
Author Information
  1. Manoj M Wagle: Computational Systems Biology Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
  2. Siqu Long: Computational Systems Biology Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
  3. Carissa Chen: Computational Systems Biology Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
  4. Chunlei Liu: Computational Systems Biology Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
  5. Pengyi Yang: Computational Systems Biology Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia. ORCID

Abstract

MOTIVATION: Single-cell omics technologies have enabled the quantification of molecular profiles in individual cells at an unparalleled resolution. Deep learning, a rapidly evolving sub-field of machine learning, has instilled a significant interest in single-cell omics research due to its remarkable success in analysing heterogeneous high-dimensional single-cell omics data. Nevertheless, the inherent multi-layer nonlinear architecture of deep learning models often makes them 'black boxes' as the reasoning behind predictions is often unknown and not transparent to the user. This has stimulated an increasing body of research for addressing the lack of interpretability in deep learning models, especially in single-cell omics data analyses, where the identification and understanding of molecular regulators are crucial for interpreting model predictions and directing downstream experimental validations.
RESULTS: In this work, we introduce the basics of single-cell omics technologies and the concept of interpretable deep learning. This is followed by a review of the recent interpretable deep learning models applied to various single-cell omics research. Lastly, we highlight the current limitations and discuss potential future directions.

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Grants

  1. 1173469/National Health and Medical Research Council

MeSH Term

Single-Cell Analysis
Deep Learning
Humans
Computational Biology
Genomics

Word Cloud

Created with Highcharts 10.0.0omicslearningsingle-celldeepresearchmodelstechnologiesmoleculardataoftenpredictionsinterpretableMOTIVATION:Single-cellenabledquantificationprofilesindividualcellsunparalleledresolutionDeeprapidlyevolvingsub-fieldmachineinstilledsignificantinterestdueremarkablesuccessanalysingheterogeneoushigh-dimensionalNeverthelessinherentmulti-layernonlineararchitecturemakes'blackboxes'reasoningbehindunknowntransparentuserstimulatedincreasingbodyaddressinglackinterpretabilityespeciallyanalysesidentificationunderstandingregulatorscrucialinterpretingmodeldirectingdownstreamexperimentalvalidationsRESULTS:workintroducebasicsconceptfollowedreviewrecentappliedvariousLastlyhighlightcurrentlimitationsdiscusspotentialfuturedirectionsInterpretable

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