SigFuge: single gene clustering of RNA-seq reveals differential isoform usage among cancer samples

Nucleic Acids Research
Patrick K KimesD Neil Hayes

Abstract

High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attent...Continue Reading

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Sep 1, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Jeremy T-H ChangR Stephanie Huang
Apr 1, 2018·Biological Chemistry·Woodys Lenga Ma BondaPascale Reverdiau
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Jan 14, 2021·Nature Communications·Hyo Young ChoiD Neil Hayes

Related Concepts

KLK12 protein, human
FAM64A protein, human
Squamous Cell Carcinoma of the Head and Neck
Squamous Cell Carcinoma
Carrier Proteins
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Cancer of Neck
Padutin
Malignant Neoplasm of Lung
Malignant Neoplasms

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