Defining the characteristics of interferon-alpha–stimulated human genes: insight from expression data and machine learning

Chai, H., Gu, Q. , Robertson, D. L. and Hughes, J. (2022) Defining the characteristics of interferon-alpha–stimulated human genes: insight from expression data and machine learning. GigaScience, 11, giac103. (doi: 10.1093/gigascience/giac103) (PMID:36399061) (PMCID:PMC9673497)

[img] Text
281882.pdf - Published Version
Available under License Creative Commons Attribution.



Background: A virus-infected cell triggers a signalling cascade, resulting in the secretion of interferons (IFNs), which in turn induces the upregulation of the IFN-stimulated genes (ISGs) that play a role in antipathogen host defence. Here, we conducted analyses on large-scale data relating to evolutionary gene expression, sequence composition, and network properties to elucidate factors associated with the stimulation of human genes in response to IFN-α. Results: We find that ISGs are less evolutionary conserved than genes that are not significantly stimulated in IFN experiments (non-ISGs). ISGs show obvious depletion of GC content in the coding region. This influences the representation of some compositions following the translation process. IFN-repressed human genes (IRGs), downregulated genes in IFN experiments, can have similar properties to the ISGs. Additionally, we design a machine learning framework integrating the support vector machine and novel feature selection algorithm that achieves an area under the receiver operating characteristic curve (AUC) of 0.7455 for ISG prediction. Its application in other IFN systems suggests the similarity between the ISGs triggered by type I and III IFNs. Conclusions: ISGs have some unique properties that make them different from the non-ISGs. The representation of some properties has a strong correlation with gene expression following IFN-α stimulation, which can be used as a predictive feature in machine learning. Our model predicts several genes as putative ISGs that so far have shown no significant differential expression when stimulated with IFN-α in the cell/tissue types in the available databases. A web server implementing our method is accessible at The docker image at can be downloaded to reproduce the prediction.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Hughes, Dr Joseph and Gu, Dr Quan and Robertson, Professor David and Chai, Haiting
Authors: Chai, H., Gu, Q., Robertson, D. L., and Hughes, J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:GigaScience
Publisher:Oxford University Press
ISSN (Online):2047-217X
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in GigaScience 11: giac103
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5281/zenodo.7244224

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research