Functional Prediction of Hypothetical Proteins from Shigella flexneri and Validation of the Predicted Models by Using ROC Curve Analysis

Abstract

Shigella spp. constitutes some of the key pathogens responsible for the global burden of diarrhoeal disease. With over 164 million reported cases per annum, shigellosis accounts for 1.1 million deaths each year. Majority of these cases occur among the children of the developing nations and the emergence of multi-drug resistance Shigella strains in clinical isolates demands the development of better/new drugs against this pathogen. The genome of Shigella flexneri was extensively analyzed and found 4,362 proteins among which the functions of 674 proteins, termed as hypothetical proteins (HPs) had not been previously elucidated. Amino acid sequences of all these 674 HPs were studied and the functions of a total of 39 HPs have been assigned with high level of confidence. Here we have utilized a combination of the latest versions of databases to assign the precise function of HPs for which no experimental information is available. These HPs were found to belong to various classes of proteins such as enzymes, binding proteins, signal transducers, lipoprotein, transporters, virulence and other proteins. Evaluation of the performance of the various computational tools conducted using receiver operating characteristic curve analysis and a resoundingly high average accuracy of 93.6% were obtained. Our comprehensive analysis will help to gain greater understanding for the development of many novel potential therapeutic interventions to defeat Shigella infection.

Chemoselective bicyclobutane-based mass spectrometric detection of biological thiols uncovers human and bacterial metabolites

“…71 For the other two pathogenic bacteria, Shigella and Salmonella, only the bifunctional enzyme glutathionylspermidine synthetase/amidase has been identified without any experimental isolation of Gsp. 72,73 The chemical structure of glutathionylspermidine was validated using MS/MS fragmentation analysis at confidence level 2 due to the lack of an internal standard. The mass spectrometric fragments of the tag, as well as the specific fragments for the conjugated Gsp were detected (Fig.…”

Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of Shigella flexneri: Emphasis on Selecting Targets for Virulence and Vaccine Design Studies

“…A vaccine for Shigella has not yet been licensed, partly because of the large repertoire of its serotypes that need to be targeted in order for the vaccine to be globally effective. Because of the rise in the cost of treatment, increased antibiotic resistance and the tenacity of poor hygiene and sanitation problems, the efficacy of existing antimicrobial treatments has been compromised [20].…”

An Educational Bioinformatics Project to Improve Genome Annotation

“…Reports estimated that around 33% of National Center for Biotechnology Information (NCBI) knowledgebase sequences in 2006 were HPs ( Kolker et al, 2004 ; Sivashankari and Shanmughavel, 2006 ; Omeershffudin and Kumar, 2019 ). While the exact number of HPs in today’s NCBI is unknown, recent papers on Mycobacterium tuberculosis and Exiguobacterium antarcticum strain B7 genomes report around 27% HPs ( da Costa et al, 2018 ; Yang et al, 2019 ) with 16% HPs in Shigella flexneri ( Gazi et al, 2018 ). Assuming 20% of the current 218,642,238 GenBank sequences are HPs, over 43 million proteins need proper annotation, and this number continues to grow exponentially as sequences continue to be deposited.…”