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2017 ; 114
(45
): E9740-E9749
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Framework and resource for more than 11,000 gene-transcript-protein-reaction
associations in human metabolism
#MMPMID29078384
Ryu JY
; Kim HU
; Lee SY
Proc Natl Acad Sci U S A
2017[Nov]; 114
(45
): E9740-E9749
PMID29078384
show ga
Alternative splicing plays important roles in generating different transcripts
from one gene, and consequently various protein isoforms. However, there has been
no systematic approach that facilitates characterizing functional roles of
protein isoforms in the context of the entire human metabolism. Here, we present
a systematic framework for the generation of gene-transcript-protein-reaction
associations (GeTPRA) in the human metabolism. The framework in this study
generated 11,415 GeTPRA corresponding to 1,106 metabolic genes for both principal
and nonprincipal transcripts (PTs and NPTs) of metabolic genes. The framework
further evaluates GeTPRA, using a human genome-scale metabolic model (GEM) that
is biochemically consistent and transcript-level data compatible, and
subsequently updates the human GEM. A generic human GEM, Recon 2M.1, was
developed for this purpose, and subsequently updated to Recon 2M.2 through the
framework. Both PTs and NPTs of metabolic genes were considered in the framework
based on prior analyses of 446 personal RNA-Seq data and 1,784 personal GEMs
reconstructed using Recon 2M.1. The framework and the GeTPRA will contribute to
better understanding human metabolism at the systems level and enable further
medical applications.