Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions

Kidane, Yared H.; Lawrence, Christopher B.; Murali, T. M.

Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions

dc.contributor.author	Kidane, Yared H.	en
dc.contributor.author	Lawrence, Christopher B.	en
dc.contributor.author	Murali, T. M.	en
dc.contributor.department	Biological Sciences	en
dc.contributor.department	Computer Science	en
dc.contributor.department	Fralin Life Sciences Institute	en
dc.contributor.department	Institute for Critical Technology and Applied Science	en
dc.date.accessioned	2014-04-05T23:32:19Z	en
dc.date.available	2014-04-05T23:32:19Z	en
dc.date.issued	2013-10-07	en
dc.date.updated	2014-04-05T23:32:20Z	en
dc.description.abstract	Background Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host’s tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host’s tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. Results In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Conclusions Our computational approaches and methodologies described here can now be applied to newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc	en
dc.description.version	Published version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	BMC Microbiology. 2013 Oct 07;13(1):224	en
dc.identifier.doi	https://doi.org/10.1186/1471-2180-13-224	en
dc.identifier.uri	http://hdl.handle.net/10919/46983	en
dc.language.iso	en	en
dc.rights	Creative Commons Attribution 4.0 International	en
dc.rights.holder	Yared H Kidane et al.; licensee BioMed Central Ltd.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.title	Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions	en
dc.title.serial	BMC Microbiology	en
dc.type	Article - Refereed	en
dc.type.dcmitype	Text	en