Abstract

The Sequence Read Archive (SRA) is a large public repository that stores raw next-generation sequencing data from thousands of diverse scientific investigations. Despite its promise, reuse and re-analysis of SRA data has been challenged by the heterogeneity and poor quality of the metadata that describe its biological samples. Recently, the MetaSRA project standardized these metadata by annotating each sample with terms from biomedical ontologies. In this work, we present a pair of Jupyter notebook-based tools that utilize the MetaSRA for building structured datasets from the SRA in order to facilitate secondary analyses of the SRA's human RNA-seq data. The first tool, called the Case-Control Finder, finds suitable case and control samples for a given disease or condition where the cases and controls are matched by tissue or cell type. The second tool, called the Series Finder, finds ordered sets of samples for the purpose of addressing biological questions pertaining to changes over a numerical property such as time. These tools were the result of a three-day-long NCBI Codeathon in March 2019 held at the University of North Carolina at Chapel Hill.

Highlights

  • The Sequence Read Archive (SRA; Leinonen et al, 2011) is a large public repository that stores next-generation sequencing data from thousands of diverse scientific investigations

  • Reuse and re-analysis of SRA data has been challenged by the heterogeneity and poor quality of the metadata that describe its biological samples (Gonçalves & Musen, 2019)

  • The MetaSRA is not capable of searching for samples associated with a particular condition and/or tissue-type that are ordered according to a numeric property

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Summary

Introduction

The Sequence Read Archive (SRA; Leinonen et al, 2011) is a large public repository that stores next-generation sequencing data from thousands of diverse scientific investigations. Reuse and re-analysis of SRA data has been challenged by the heterogeneity and poor quality of the metadata that describe its biological samples (Gonçalves & Musen, 2019). The MetaSRA project (Bernstein et al, 2017) standardized these metadata by annotating each sample with terms from biomedical ontologies including Cell Ontology (Bard et al, 2005), Uberon (Mungall et al, 2012), Disease Ontology (Schriml et al, 2019), Cellosaurus (Bairoch, 2018), and the Experimental Factors Ontology (Malone et al, 2010). The MetaSRA web interface is not capable of producing structured datasets such as those that match case samples associated with a target condition or disease with healthy control samples. The MetaSRA is not capable of searching for samples associated with a particular condition and/or tissue-type that are ordered according to a numeric property (e.g., age)

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