Evidence map›Paper›PMID 31286861›Full record

ArticleBMC bioinformatics2019

Deconvolution of autoencoders to learn biological regulatory modules from single cell mRNA sequencing data.

Savvas Kinalis, Finn Cilius Nielsen, Ole Winther, Frederik Otzen Bagger

Abstract read
In one paragraph

Article in BMC bioinformatics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. Interpretable deep learning in single-cell omics.Bioinformatics (Oxford, England) · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Savvas KinalisCentre for Genomic Medicine Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Finn Cilius NielsenCentre for Genomic Medicine Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Ole WintherCentre for Genomic Medicine Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Frederik Otzen BaggerCentre for Genomic Medicine Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. frederik@binf.ku.dk.ORCID http://orcid.org/0000-0003-0636-8845

Funding

Rigshospitalet R159-A6890
6 · The paper itself

Abstract

backgroundUnsupervised machine learning methods (deep learning) have shown their usefulness with noisy single cell mRNA-sequencing data (scRNA-seq), where the models generalize well, despite the zero-inflation of the data. A class of neural networks, namely autoencoders, has been useful for denoising of single cell data, imputation of missing values and dimensionality reduction.

resultsHere, we present a striking feature with the potential to greatly increase the usability of autoencoders: With specialized training, the autoencoder is not only able to generalize over the data, but also to tease apart biologically meaningful modules, which we found encoded in the representation layer of the network. Our model can, from scRNA-seq data, delineate biological meaningful modules that govern a dataset, as well as give information as to which modules are active in each single cell. Importantly, most of these modules can be explained by known biological functions, as provided by the Hallmark gene sets.

conclusionsWe discover that tailored training of an autoencoder makes it possible to deconvolute biological modules inherent in the data, without any assumptions. By comparisons with gene signatures of canonical pathways we see that the modules are directly interpretable. The scope of this discovery has important implications, as it makes it possible to outline the drivers behind a given effect of a cell. In comparison with other dimensionality reduction methods, or supervised models for classification, our approach has the benefit of both handling well the zero-inflated nature of scRNA-seq, and validating that the model captures relevant information, by establishing a link between input and decoded data. In perspective, our model in combination with clustering methods is able to provide information about which subtype a given single cell belongs to, as well as which biological functions determine that membership.

Indexed as

Neural Networks, ComputerUnsupervised Machine LearningCluster AnalysisGene Expression ProfilingRNA, MessengerSequence Analysis, RNASingle-Cell AnalysisRNA, MessengerBiological pathway analysisDeep learningExpression profilesFunctional analysisGene set enrichment analysisInterpretable machine learningManifold learningNeural networksSingle-cell RNA-sequencing

Identifiers

PMID31286861
PMCPMC6615267

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.