Dataset Information

BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty.

ABSTRACT: Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly model the variability between samples and treats the transcript allocation of reads as latent variables. We perform an extensive benchmark across both simulated and experimental RNA-seq datasets, where BANDITS has extremely favourable performance with respect to the competitors considered.

SUBMITTER: Tiberi S

PROVIDER: S-EPMC7075019 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty.

Tiberi Simone S Robinson Mark D MD

Genome biology 20200316 1

Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly model the variability between samples and treats the transcript allocation of reads as latent var ...[more]

PMID: 32178699

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Project description:BackgroundStatistical inference based on small datasets, commonly found in precision oncology, is subject to low power and high uncertainty. In these settings, drawing strong conclusions about future research utility is difficult when using standard inferential measures. It is therefore important to better quantify the uncertainty associated with both significant and non-significant results based on small sample sizes.MethodsWe developed a new method, Bayesian Additional Evidence (BAE), that determines (1) how much additional supportive evidence is needed for a non-significant result to reach Bayesian posterior credibility, or (2) how much additional opposing evidence is needed to render a significant result non-credible. Although based in Bayesian analysis, a prior distribution is not needed; instead, the tipping point output is compared to reasonable effect ranges to draw conclusions. We demonstrate our approach in a comparative effectiveness analysis comparing two treatments in a real world biomarker-defined cohort, and provide guidelines for how to apply BAE in practice.ResultsOur initial comparative effectiveness analysis results in a hazard ratio of 0.31 with 95% confidence interval (0.09, 1.1). Applying BAE to this result yields a tipping point of 0.54; thus, an observed hazard ratio of 0.54 or smaller in a replication study would result in posterior credibility for the treatment association. Given that effect sizes in this range are not extreme, and that supportive evidence exists from a similar published study, we conclude that this problem is worthy of further research.ConclusionsOur proposed method provides a useful framework for interpreting analytic results from small datasets. This can assist researchers in deciding how to interpret and continue their investigations based on an initial analysis that has high uncertainty. Although we illustrated its use in estimating parameters based on time-to-event outcomes, BAE easily applies to any normally-distributed estimator, such as those used for analyzing binary or continuous outcomes.

Dataset Information

BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty.

Publications

BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty.

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