Machine learning analysis of gene expression data reveals novel diagnostic and prognostic biomarkers and identifies therapeutic targets for soft tissue sarcomas

PLoS Computational Biology
David G P van IJzendoornJudith V M G Bovée

Abstract

Based on morphology it is often challenging to distinguish between the many different soft tissue sarcoma subtypes. Moreover, outcome of disease is highly variable even between patients with the same disease. Machine learning on transcriptome sequencing data could be a valuable new tool to understand differences between and within entities. Here we used machine learning analysis to identify novel diagnostic and prognostic markers and therapeutic targets for soft tissue sarcomas. Gene expression data was used from the Cancer Genome Atlas, the Genotype-Tissue Expression project and the French Sarcoma Group. We identified three groups of tumors that overlap in their molecular profiles as seen with unsupervised t-Distributed Stochastic Neighbor Embedding clustering and a deep neural network. The three groups corresponded to subtypes that are morphologically overlapping. Using a random forest algorithm, we identified novel diagnostic markers for soft tissue sarcoma that distinguished between synovial sarcoma and MPNST, and that we validated using qRT-PCR in an independent series. Next, we identified prognostic genes that are strong predictors of disease outcome when used in a k-nearest neighbor algorithm. The prognostic genes were f...Continue Reading

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Citations

May 24, 2019·PLoS Computational Biology·Jason A Papin, Feilim Mac Gabhann
Dec 1, 2019·Genes·Sandra BrasilAnd Gonçalo Valadão
Mar 11, 2020·Cancers·Wan ZhuXiangqian Guo
Jun 20, 2020·Clinical Pharmacology and Therapeutics·Sebastien Benzekry
May 10, 2020·The European Respiratory Journal·Konstantinos P ExarchosKonstantinos Kostikas
Jul 23, 2020·Molecular Diagnosis & Therapy·Aikaterini MastorakiEmmanouil Pikoulis
Feb 19, 2021·Computational and Structural Biotechnology Journal·Taoyu YeYang Zhang
Apr 6, 2021·PLoS Computational Biology·Rasool SaghaleyniJonathan L Robinson
May 1, 2021·International Journal of Molecular Sciences·Marco Del GiudiceMatteo Cereda
May 21, 2021·Skeletal Radiology·Matthew D LiConnie Y Chang
Apr 8, 2021·Histopathology·Suk Wai LamJudith V M G Bovée

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Datasets Mentioned

BETA
GSE21050

Methods Mentioned

BETA
PCA
RNA-seq
PCR
ChIP-seq

Software Mentioned

ImageJ
igraph
Maxstat
Keras
Caret
GEOquery
EnrichR
Limma
Kinase Enrichment Analysis
TensorFlow

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