Functional assignment to hypothetical proteins in Orientia tsutsugamushistrain Ikeda.

Bioinformation. 2022; 18(3): 188–195. Published online 2022 Mar 31. doi: 10.6026/97320630018188 PMCID: PMC9722422 PMID: 36518125 Functional assignment to hypothetical proteins in Orientia tsutsugamushistrain Ikeda Dixit Sharma,1,* Sunil Kumar,1 Ankita Sharma,2 Rakesh Kumar,1 Ranjit Kumar,1 Mahesh Kulharia,2 and Manish Kumar3 Dixit Sharma 1Department of Animal Sciences, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Dixit Sharma Sunil Kumar 1Department of Animal Sciences, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Sunil Kumar Ankita Sharma 2Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Ankita Sharma Rakesh Kumar 1Department of Animal Sciences, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Rakesh Kumar Ranjit Kumar 1Department of Animal Sciences, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Ranjit Kumar Mahesh Kulharia 2Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Mahesh Kulharia Manish Kumar 3Department of Chemistry and Chemical Sciences, School of Physical and Material Science, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 Find articles by Manish Kumar Author information Article notes Copyright and License information Disclaimer 1Department of Animal Sciences, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 2Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 3Department of Chemistry and Chemical Sciences, School of Physical and Material Science, Central University of Himachal Pradesh, District Kangra, Himachal Pradesh, India - 176206 *Dixit Sharma ni.ca.ucph@71tixidamrahs, moc.liamg@71tixidamrahs Received 2021 Oct 21; Revised 2022 Mar 11; Accepted 2022 Mar 31. Copyright © 2022 Biomedical Informatics This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. Abstract Orientia tsutsugamushi(O. tsutsugamushi) is an intracellular bacterial pathogen which causes zoonosis scrub typhus in humans. Genome of O. tsutsugamushi strain Ikeda contains 214 hypothetical proteins (HPs) which is nearly 20% of the total proteins. Domain and family based functional analysis of HPs results in the annotation of 44 hypothetical proteins. The annotated HPs were classified in to five main classes namely, gene expression and regulation, transport, metabolism, cell signaling and proteolysis. Thus, computational analysis of HPs helps to understand their putative roles in various biological and cellular processes, including pathogenesis for further consideration as potential therapeutic targets. Keywords: Orientia tsutsugamushi, hypothetical proteins, therapeutic targets Background: Orientia tsutsugamushi(O. tsutsugamushi) is an obligate intracellular pathogen responsible for infectious illness scrub typhus in humans. The zoonotic disease scrub typhus is a vector borne disease transmitted to human through the bite of Leptotrombidium mite larvae. The disease is predominant in Asia-Pacific region but the cases from Middle East and South America showed the wide geographical distribution of pathogen [1-2]. Scrub typhus in South East Asia is most important emerging infectious zoonotic disease and most common rickettsial disease in India. The outbreak of the disease was reported in different provinces in India including Assam, Himachal Pradesh, Jammu and Kashmir, Bihar, Rajasthan, Tamilnadu and may more [3]. The infection of O. tsutsugamushi can also lead to multiorgan failure and other disease like neurological complications, Parkinson's disease, acute kidney injury and acute respiratory distress syndrome [4-6]. Due to high mortality and non-specific representation of disease the effectual control measure are needed. Earlier attempts were made to prioritize metabolic pathway proteins and metal-binding proteins of O. tsutsugamushi as potential therapeutic targets [7-8]. The experimental techniques are very useful but expensive and time consuming whereas computational techniques evolved as most promising and reliable approaches for dissecting the genome or proteome sequence datasets[9,10]. Earlier, computational methods were efficiently used for deciphering the whole proteome data of different bacterial pathogens [11,12]. Therefore, it is of interest to document data on the functional assignment to hypothetical proteins (HPs) in Orientia tsutsugamushistrain Ikeda for further consideration in drug development. Methodology: Hypothetical proteins dataset retrieval: The complete proteome dataset of O. tsutsugamushi strain Ikeda was downloaded from Ref Seq server. Further, the HPs were extracted by searching the term "hypothetical proteins" in the whole proteins dataset. Functional prediction: Functional conserved signature sequences or domains of HPs were predicted by Inter Pro Scan [13] and Pfam [14]. Inter Pro Scan allows protein sequence to search against Inter Pro's signatures i.e., predicted models that define families, domains and sites of the proteins. Pfam is the collection of curated protein families with clearly described organization of domains. Metabolic pathway analysis: Blast KOALA [15] at Kyoto Encylcopedia of Genes and Genomes (KEGG) was used for the analysis of metabolic pathways of HPs. KEGG is integrated database for biological interpretation of genomic and other high throughput sequence data. Sub-cellular localization prediction: The subcellular localization of HPs were investigated by SOSUIGramN [16]. SOSUIGramN predict subcellular localization on the basis of physiochemical parameters of N- and C-terminal signal sequence and total sequence. The overall accuracy of the software is 92.9%. Identification of potential therapeutic targets among HPs: To extract non-homologous proteins of O. tsutsugamushi, BLASTp [17] search of HPs was performed against host (human; taxid: 9906) proteins at NCBI with expect value (E-value) 10-5. Bacterial toxins are described as most potent targets for drug discovery process. Essentiality of HPs was checked with the help of Database of Essential Genes (DEG) version 10 (...truncated)