Genome-Wide Functional Annotation of Human Protein-Coding Splice Variants Using Multiple Instance Learning.

Abstract:

:The vast majority of human multiexon genes undergo alternative splicing and produce a variety of splice variant transcripts and proteins, which can perform different functions. These protein-coding splice variants (PCSVs) greatly increase the functional diversity of proteins. Most functional annotation algorithms have been developed at the gene level; the lack of isoform-level gold standards is an important intellectual limitation for currently available machine learning algorithms. The accumulation of a large amount of RNA-seq data in the public domain greatly increases our ability to examine the functional annotation of genes at isoform level. In the present study, we used a multiple instance learning (MIL)-based approach for predicting the function of PCSVs. We used transcript-level expression values and gene-level functional associations from the Gene Ontology database. A support vector machine (SVM)-based 5-fold cross-validation technique was applied. Comparatively, genes with multiple PCSVs performed better than single PCSV genes, and performance also improved when more examples were available to train the models. We demonstrated our predictions using literature evidence of ADAM15, LMNA/C, and DMXL2 genes. All predictions have been implemented in a web resource called "IsoFunc", which is freely available for the global scientific community through http://guanlab.ccmb.med.umich.edu/isofunc .

journal_name

J Proteome Res

authors

Panwar B,Menon R,Eksi R,Li HD,Omenn GS,Guan Y

doi

10.1021/acs.jproteome.5b00883

subject

Has Abstract

pub_date

2016-06-03 00:00:00

pages

1747-53

issue

6

eissn

1535-3893

issn

1535-3907

journal_volume

15

pub_type

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