{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:46:59Z","timestamp":1790567219476,"version":"4.1.0"},"reference-count":114,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T00:00:00Z","timestamp":1590192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000199","name":"USDA","doi-asserted-by":"publisher","award":["# 2016\u201370016-24781"],"award-info":[{"award-number":["# 2016\u201370016-24781"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aerobic, Gram-negative motile bacillus, Burkholderia pseudomallei is a facultative intracellular bacterium causing melioidosis, a critical disease of public health importance, which is widely endemic in the tropics and subtropical regions of the world. Melioidosis is associated with high case fatality rates in animals and humans; even with treatment, its mortality is 20\u201350%. It also infects plants and is designated as a biothreat agent. B. pseudomallei is pathogenic due to its ability to invade, resist factors in serum and survive intracellularly. Despite its importance, to date only a few effector proteins have been functionally characterized, and there is not much information regarding the host\u2013pathogen protein\u2013protein interactions (PPI) of this system, which are important to studying infection mechanisms and thereby develop prevention measures. We explored two computational approaches, the homology-based interolog and the domain-based method, to predict genome-scale host\u2013pathogen interactions (HPIs) between two different strains of B. pseudomallei (prototypical, and highly virulent) and human. In total, 76\u00a0335 common HPIs (between the two strains) were predicted involving 8264 human and 1753 B. pseudomallei proteins. Among the unique PPIs, 14\u00a0131 non-redundant HPIs were found to be unique between the prototypical strain and human, compared to 3043 non-redundant HPIs between the highly virulent strain and human. The protein hubs analysis showed that most B. pseudomallei proteins formed a hub with human dnaK complex proteins associated with tuberculosis, a disease similar in symptoms to melioidosis. In addition, drug-binding and carbohydrate-binding mechanisms were found overrepresented within the host\u2013pathogen network, and metabolic pathways were frequently activated according to the pathway enrichment. Subcellular localization analysis showed that most of the pathogen proteins are targeting human proteins inside cytoplasm and nucleus. We also discovered the host targets of the drug-related pathogen proteins and proteins that form T3SS and T6SS in B. pseudomallei. Additionally, a comparison between the unique PPI patterns present in the prototypical and highly virulent strains was performed. The current study is the first report on developing a genome-scale host\u2013pathogen protein interaction networks between the human and B. pseudomallei, a critical biothreat agent. We have identified novel virulence factors and their interacting partners in the human proteome. These PPIs can be further validated by high-throughput experiments and may give new insights on how B. pseudomallei interacts with its host, which will help medical researchers in developing better prevention measures.<\/jats:p>","DOI":"10.1093\/bib\/bbz162","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T12:09:58Z","timestamp":1574338198000},"source":"Crossref","is-referenced-by-count":27,"title":["<i>In silico<\/i>prediction of host\u2013pathogen protein interactions in melioidosis pathogen<i>Burkholderia pseudomallei<\/i>and human reveals novel virulence factors and their targets"],"prefix":"10.1093","volume":"22","author":[{"given":"Cristian D","family":"Loaiza","sequence":"first","affiliation":[{"name":"Center for Integrated BioSystems\/Department of Plants, Soils, and Climate, College of Agriculture and Applied Sciences, Utah State University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Duhan","sequence":"additional","affiliation":[{"name":"Center for Integrated BioSystems\/Department of Plants, Soils, and Climate, College of Agriculture and Applied Sciences, Utah State University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Lister","sequence":"additional","affiliation":[{"name":"Bioinformatics Facility, Center for Integrated BioSystems, Utah State University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-1240","authenticated-orcid":false,"given":"Rakesh","family":"Kaundal","sequence":"additional","affiliation":[{"name":"Department of Plants, Soils, and Climate\/Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322 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\u2018Interologs\u2019","volume":"11","author":"Matthews","year":"2001","journal-title":"Genome Res"},{"key":"2021052613335216600_ref23","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btg118","article-title":"Integrative approach for computationally inferring protein domain interactions","volume":"19","author":"Ng","year":"2003","journal-title":"Bioinformatics"},{"key":"2021052613335216600_ref24","doi-asserted-by":"crossref","first-page":"i159","DOI":"10.1093\/bioinformatics\/btm208","article-title":"Computational prediction of host-pathogen protein\u2013protein interactions","volume":"23","author":"Dyer","year":"2007","journal-title":"Bioinformatics"},{"key":"2021052613335216600_ref25","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1093\/nar\/gkl219","article-title":"Prediction of yeast protein-protein interaction network: insights from the gene ontology and annotations","volume":"34","author":"Wu","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2021052613335216600_ref26","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1110\/ps.073228407","article-title":"Host-pathogen protein interactions predicted by comparative modeling","volume":"16","author":"Davis","year":"2007","journal-title":"Protein Sci"},{"key":"2021052613335216600_ref27","doi-asserted-by":"crossref","first-page":"W331","DOI":"10.1093\/nar\/gki585","article-title":"PRISM: protein interactions by structural matching","volume":"33","author":"Ogmen","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2021052613335216600_ref28","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1007\/s00726-011-0978-z","article-title":"Prediction of protein\u2013protein interactions between Ralstonia solanacearum and Arabidopsis thaliana","volume":"42","author":"Li","year":"2012","journal-title":"Amino 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Computational methods to predict protein and domain interaction partners","volume":"3","author":"Shoemaker","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"2021052613335216600_ref32","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1186\/1752-0509-7-S6-S6","article-title":"Stringent DDI-based prediction of H. sapiens\u2013M. tuberculosis H37Rv protein\u2013protein interactions","volume":"7","author":"Zhou","year":"2013","journal-title":"BMC Syst Biol"},{"key":"2021052613335216600_ref33","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1093\/bioinformatics\/btn524","article-title":"The Burkholderia genome database: facilitating flexible queries and comparative analyses","volume":"24","author":"Winsor","year":"2008","journal-title":"Bioinformatics"},{"key":"2021052613335216600_ref34","doi-asserted-by":"crossref","first-page":"baw103","DOI":"10.1093\/database\/baw103","article-title":"HPIDB 2.0: a curated database for host-pathogen 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Res"},{"key":"2021052613335216600_ref38","doi-asserted-by":"crossref","first-page":"D369","DOI":"10.1093\/nar\/gkw1102","article-title":"The BioGRID interaction database: 2017 update","volume":"45","author":"Chatr-Aryamontri","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2021052613335216600_ref39","doi-asserted-by":"crossref","first-page":"D281","DOI":"10.1093\/nar\/gkm960","article-title":"The Pfam protein families database","volume":"36","author":"Finn","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2021052613335216600_ref40","doi-asserted-by":"crossref","first-page":"D374","DOI":"10.1093\/nar\/gkt887","article-title":"3did: a catalog of domain-based interactions of known three-dimensional structure","volume":"42","author":"Mosca","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2021052613335216600_ref41","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1186\/1477-5956-10-S1-S9","article-title":"IDDI: integrated domain-domain interaction and protein interaction analysis system","volume":"10","author":"Kim","year":"2012","journal-title":"Proteome Sci"},{"key":"2021052613335216600_ref42","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1101\/gr.1774904","article-title":"Annotation transfer between genomes: protein\u2013protein interologs and protein\u2013DNA regulogs","volume":"14","author":"Yu","year":"2004","journal-title":"Genome Res"},{"key":"2021052613335216600_ref43","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2021052613335216600_ref44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2017.00128","article-title":"Computational analysis of host\u2013pathogen protein interactions between humans and different strains of enterohemorrhagic Escherichia coli","volume":"7","author":"Bose","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"2021052613335216600_ref45","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/bib\/bbx132","article-title":"Prediction of protein\u2013protein interactions between fungus (Magnaporthe grisea) and rice (Oryza sativa L.)","volume":"20","author":"Ma","year":"2017","journal-title":"Brief Bioinform"},{"key":"2021052613335216600_ref46","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/bioinformatics\/14.9.755","article-title":"Profile hidden Markov models","volume":"14","author":"Eddy","year":"1998","journal-title":"Bioinformatics"},{"key":"2021052613335216600_ref47","doi-asserted-by":"crossref","first-page":"S296","DOI":"10.1093\/bioinformatics\/17.suppl_1.S296","article-title":"Protein\u2013protein interaction map inference using interacting domain profile pairs","volume":"17","author":"Wojcik","year":"2001","journal-title":"Bioinformatics"},{"key":"2021052613335216600_ref48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/819528","article-title":"The domain landscape of virus-host interactomes","volume":"2014","author":"Zheng","year":"2014","journal-title":"Biomed Res Int"},{"key":"2021052613335216600_ref49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40203-017-0021-5","article-title":"Study of intra-inter species protein-protein interactions for potential drug targets identification and subsequent drug design for Escherichia coli O104:H4 C277-11","volume":"5","author":"Mondal","year":"2016","journal-title":"Silico Pharmacol"},{"key":"2021052613335216600_ref50","doi-asserted-by":"crossref","first-page":"bau079","DOI":"10.1093\/database\/bau079","article-title":"PlantCAZyme: a database for plant carbohydrate-active enzymes","volume":"2014","author":"Ekstrom","year":"2014","journal-title":"Database"},{"key":"2021052613335216600_ref51","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/pro.3307","article-title":"The human protein atlas: a spatial map of the human proteome","volume":"27","author":"Thul","year":"2018","journal-title":"Protein Sci"},{"key":"2021052613335216600_ref52","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1093\/bioinformatics\/btw723","article-title":"Hum-mPLoc 3.0: prediction enhancement of human protein subcellular localization through modeling the hidden correlations of gene ontology and functional domain features","volume":"33","author":"Zhou","year":"2016","journal-title":"Bioinformatics"},{"key":"2021052613335216600_ref53","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/bioinformatics\/btq249","article-title":"PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive 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Comput Biol"},{"key":"2021052613335216600_ref57","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1186\/s13071-018-3179-8","article-title":"Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii","volume":"11","author":"Wang","year":"2018","journal-title":"Parasit Vectors"},{"key":"2021052613335216600_ref58","doi-asserted-by":"crossref","first-page":"e01193","DOI":"10.1128\/mBio.01193-19","article-title":"Determination of an interaction network between an extracellular bacterial pathogen and the human host","volume":"10","author":"Griesenauer","year":"2019","journal-title":"MBio"},{"key":"2021052613335216600_ref59","first-page":"604","article-title":"Why, when and how to adjust your P values?","volume":"20","author":"Jafari","year":"2019","journal-title":"Cell J"},{"key":"2021052613335216600_ref60","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B"},{"key":"2021052613335216600_ref61","volume-title":"org. Hs. eg. db: Genome Wide Annotation for Human","author":"Carlson"},{"key":"2021052613335216600_ref62","volume-title":"AnnotationForge: Code for Building Annotation Database Packages","author":"Carlson"},{"key":"2021052613335216600_ref63","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1038\/srep04305","article-title":"Comparative Burkholderia pseudomallei natural history virulence studies using an aerosol murine model of infection","volume":"4","author":"Massey","year":"2014","journal-title":"Sci Rep"},{"key":"2021052613335216600_ref64","volume-title":"Third International Conference on Weblogs and Social Media","author":"Bastian","year":"2009"},{"key":"2021052613335216600_ref65","first-page":"7868","article-title":"OpenOrd: an open-source toolbox for large graph layout","volume":"786806","author":"Martin","year":"2011","journal-title":"Vis Data Anal"},{"key":"2021052613335216600_ref66","first-page":"37","article-title":"Efficient, high-quality force-directed graph drawing","volume":"10","author":"Hu","year":"2005","journal-title":"Math J"},{"key":"2021052613335216600_ref67","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/spe.4380211102","article-title":"Graph drawing by force-directed placement","volume":"21","author":"Fruchterman","year":"1991","journal-title":"Softw Pract Exp"},{"key":"2021052613335216600_ref68","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/1278932","article-title":"Empirical comparison of visualization tools for larger-scale network analysis","volume":"2017","author":"Pavlopoulos","year":"2017","journal-title":"Adv Bioinformatics"},{"key":"2021052613335216600_ref69","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1128\/JB.173.6.1992-1996.1991","article-title":"Role of RpoH, a heat shock regulator protein, in Escherichia coli carbon starvation protein synthesis and survival","volume":"173","author":"Jenkins","year":"1991","journal-title":"J 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