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The shape of gene expression distributions matter: how incorporating distribution shape improves the interpretation of cancer transcriptomic data

In genomics, we often assume that continuous data, such as gene expression, follow a specific kind of distribution. However we rarely stop to question the validity of this assumption, or consider how broadly applicable it may be to all genes that are in the transcriptome. Our study investigated the...

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Published in:BMC bioinformatics 2020-12, Vol.21 (Suppl 21), p.562-18, Article 562
Main Authors: de Torrenté, Laurence, Zimmerman, Samuel, Suzuki, Masako, Christopeit, Maximilian, Greally, John M, Mar, Jessica C
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description In genomics, we often assume that continuous data, such as gene expression, follow a specific kind of distribution. However we rarely stop to question the validity of this assumption, or consider how broadly applicable it may be to all genes that are in the transcriptome. Our study investigated the prevalence of a range of gene expression distributions in three different tumor types from the Cancer Genome Atlas (TCGA). Surprisingly, the expression of less than 50% of all genes was Normally-distributed, with other distributions including Gamma, Bimodal, Cauchy, and Lognormal also represented. Most of the distribution categories contained genes that were significantly enriched for unique biological processes. Different assumptions based on the shape of the expression profile were used to identify genes that could discriminate between patients with good versus poor survival. The prognostic marker genes that were identified when the shape of the distribution was accounted for reflected functional insights into cancer biology that were not observed when standard assumptions were applied. We showed that when multiple types of distributions were permitted, i.e. the shape of the expression profile was used, the statistical classifiers had greater predictive accuracy for determining the prognosis of a patient versus those that assumed only one type of gene expression distribution. Our results highlight the value of studying a gene's distribution shape to model heterogeneity of transcriptomic data and the impact on using analyses that permit more than one type of gene expression distribution. These insights would have been overlooked when using standard approaches that assume all genes follow the same type of distribution in a patient cohort.
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subjects Analysis
Asymmetry
Biological activity
Biomarkers, Tumor - genetics
Cancer
Cancer genomics
Classification schemes
Data Interpretation, Statistical
Datasets
Gene expression
Gene Expression Profiling
Genes
Genetic aspects
Genomics
Heterogeneity
Humans
Impact analysis
Leukemia
Male
Middle Aged
Multi-modality
Neoplasms - diagnosis
Neoplasms - genetics
Non-normal distribution
Normal distribution
Patients
Prognosis
Statistical methods
Survival analysis
Transcriptomes
title The shape of gene expression distributions matter: how incorporating distribution shape improves the interpretation of cancer transcriptomic data
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