A substrate-based ontology for human solute carriers.

Molecular Systems Biology
Eva MeixnerGiulio Superti-Furga

Abstract

Solute carriers (SLCs) are the largest family of transmembrane transporters in the human genome with more than 400 members. Despite the fact that SLCs mediate critical biological functions and several are important pharmacological targets, a large proportion of them is poorly characterized and present no assigned substrate. A major limitation to systems-level de-orphanization campaigns is the absence of a structured, language-controlled chemical annotation. Here we describe a thorough manual annotation of SLCs based on literature. The annotation of substrates, transport mechanism, coupled ions, and subcellular localization for 446 human SLCs confirmed that ~30% of these were still functionally orphan and lacked known substrates. Application of a substrate-based ontology to transcriptomic datasets identified SLC-specific responses to external perturbations, while a machine-learning approach based on the annotation allowed us to identify potential substrates for several orphan SLCs. The annotation is available at https://opendata.cemm.at/gsflab/slcontology/. Given the increasing availability of large biological datasets and the growing interest in transporters, we expect that the effort presented here will be critical to provide ...Continue Reading

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Citations

Aug 19, 2020·The FEBS Journal·Mattia D PizzagalliGiulio Superti-Furga
Oct 31, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sook Wah YeeKathleen M Giacomini
Aug 28, 2021·Frontiers in Pharmacology·Vojtech DvorakGiulio Superti-Furga

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Methods Mentioned

BETA
glycosylation

Software Mentioned

Rstudio IDE
oboe R
randomForest
readr
R BiomaRt package
ggplot2
ArrayExpress
randomForest R
End Sequence Analysis Toolkit ( ESAT )
DESeq2

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