Biology subjects

Suravajhala, P.

Publications and source records attributed to Suravajhala, P..

14 recordsLinked to original sources

bioRxiv2025

Proteus mirabilis entails a switch from commensal to pathogen - Genomic insights from a blaTEM-1B-harboring novel isolate from India.

BackgroundProteus mirabilis is an opportunistic pathogen that can shift from gut commensalism to causing severe urinary tract and bloodstream infections. The genomic basis of P. mirabilis transition from commensalism to severe infection is not well understood, especially in Indian clinical isolates. This study aimed to explore the genomic attributes of a prevalent P. mirabilis strain in India. MethodsWhole-genome sequencing (WGS) was performed on a clinical P. mirabilis isolate by using NGS. AMR genes and virulence factors were identified using ResFinder/CARD and VFDB, respectively. Sequence typing was performed with MLST. Protein-protein interactions and noncoding RNAs were analyzed using STRING, CytoHubba, and BAKTA. ResultsWGS confirmed the multidrug-resistant nature of the isolate, revealing a broad repertoire of AMR genes, including blaTEM-1B, conferring resistance to beta-lactam antibiotics. Several resistance determinants were co-localised with insertion sequences on a single contig, indicating a high potential for horizontal gene transfer. The virulome profile highlighted multiple fimbrial genes, hemolysins, and toxin-encoding loci, together supporting strong adhesion, biofilm formation, and host tissue damage. Comparative analysis revealed unique genomic signatures not present in reference isolates, including additional virulence determinants and mobile genetic elements. MLST profile of the isolate is closely related to ST-675 & ST-797, while virulence typing (vST-1157) indicated a novel profile distinct from reference ST-675 strains. Insilico protein-protein interaction of this isolate revealed a highly interconnected virulence network, with urease, fimbrial adhesins, and hemolysins emerging as central functional modules driving pathogenicity. In addition, a noncoding RNA was identified within the genomic context of the ure operon (Contig 10), suggesting a possible regulatory role in urease expression. PPI network analysis highlighted urease, fimbrial proteins, and hemolysins as central hubs contributing to pathogenicity. ConclusionsThis study presents the first genomic characterization of a multidrug-resistant P. mirabilis clinical isolate from India, designated as P. mirabilis strain Indica. The convergence of AMR genes, virulence factors, MGEs and a novel noncoding RNAs linked to urease expression highlights the emergence of a high-risk variant in India. These findings have significant implications for infection control and emphasize the need for genomic surveillance to guide therapeutic strategies and develop new interventions globally.

microbiology↗

bioRxiv2024

Azole resistance: Patterns of amino acid substitutions in Candida sterol 14α-demethylase

The emergence of azole-resistant Candida infections is a major concern. A key mechanism is the gain of resistance through amino acid substitutions in the sterol 14-demethylase, the main target of azole drugs. While numerous resistant substitutions are known, the pattern of such substitutions is unclear. We hypothesized that the resistant substitutions occur disproportionately at the azole-binding sites. We compiled 2,222 instances of azole-resistant substitutions from the literature and performed extensive computational sequence analyses. Altogether there were 169 known substitutions at 133 sites in sterol 14-demethylases of seven Candida species, whereas C. albicans alone had 120 substitutions at 97 sites. Just 10 sites and 18 substitutions (such as Y132F/H, K143R, D116E, and G464S) accounted for 75% of the total instances. Only about 48% of the sites were present within the previously recognized hotspot regions, while just 33% of the known azole-interacting residues had known resistant substitutions, most of them with only a few instances. The literature data on azole-resistant substitutions in Candida appear to be highly biased as a few substitutions such as Y132F/H and K143R were preferentially sought and reported with over 1000 instances, while there were also numerous reports of "resistant" substitutions in azole-susceptible Candida isolates. Our study provides interesting perspectives into azole resistance.

bioinformatics↗

bioRxiv2023

Whole Genome Sequencing and Assembly of the House Sparrow, Passer domesticus

The common house sparrow, Passer domesticus is a small bird belonging to the family Passeridae. Here, we provide high-quality whole genome sequence data along with assembly for the house sparrow. The final genome assembly was assembled using a Shovill/SPAdes/MASURCA/BUSCO workflow, consisting of contigs spanning 268193 bases and coalescing around a 922 MB sized reference genome. We employed rigorous statistical thresholds to check the coverage, as the Passer genome showed considerable similarity to Gallus gallus (chicken) and Taeniopygia guttata (Zebra finch) genomes, also providing a functional annotation. This new annotated genome assembly will be a valuable resource as a reference for comparative and population genomic analyses of passerine, avian, and vertebrate evolution. SignificanceAvian evolution has been of great interest in the context of extinction. Annotating the genomes such as passerines would be of significant interest as we could understand the behavior/foraging traits and further explore their evolutionary landscape. In this work, we provide a full genome sequence of Indian house sparrow, viz. Passer domesticus which will serve as a useful resource in understanding the adaptability, evolution, geography, allee effects and circadian rhythms.

evolutionary biology↗

bioRxiv2023

Benchmarking whole exome sequencing pipeline for predicting pathogenic variants of significance

Benchmarking whole exome pipelines is crucial for evaluating and comparing their performance in variant calling and clinical significance annotation. It enables researchers and clinicians to assess the accuracy, sensitivity, and specificity of different pipelines and identify the most effective and reliable ones. In this study, we evaluated and compared the performance of our in-house consensus exome pipeline with a widely recognized gold standard Genome Analysis Toolkit (GATK) pipeline. Four datasets were used for evaluation, three 1000 Genome Project (1KGP) datasets and one Prostate cancer (PCa) Sample. The consensus pipeline consistently demonstrated a higher average transition-to-transversion (Ti/Tv) ratio, indicating enhanced precision in identifying single nucleotide variant (SNV) calls. This suggests that the consensus pipeline excels in effectively discerning true genetic variations from sequencing artefacts, particularly in the context of exome sequencing. Additionally, the pipeline exhibited increased sensitivity in detecting pathogenic and likely pathogenic variants in the PCa sample, further highlighting its efficacy in identifying clinically relevant variants. We also conducted a trio exome analysis with the use of two trio pipelines, viz. VarScan Trio and GATK joint calling pipelines on our erstwhile Congenital Pouch Colon (CPC) samples from our rare disease cohort which we published earlier and found that the GATK predicted a significantly higher number of variants compared to VarScan. From our pipeline, viz. CONVEX: Consensus Variant Pipeline for Exome Analysis we developed, our study demonstrates a large potential for trio-variant calling analysis paving the way for precision medicine. We discuss the impending benchmark results using the CONVEX.

bioinformatics↗

bioRxiv2023

In silico approaches to identify the role of lncRNAs in Prostate cancer and Androgen receptor-targeted proteins

Long non-coding RNA (lncRNAs) are known to have a role in pathogenesis of a broad spectrum of malignancies.These are found to have a significant role as signal transduction mediators in cancer signaling pathways. Prostate Cancer (PCa) is emerging with increasing cases worldwide even as advanced approaches in clinical diagnosis and treatment of PCa are still challenging to address. To enhance patient stratification, there is an indefatigable need to understand risk that can allow new approaches of treatment based on prognosis. While PCa is known to have mediated androgen receptor (AR) stimulation, the latter plays a key role in regulating transcription of genes via nuclear translocation which in turn leads to response to androgens. LncRNAs have been implicated in developing clinical diagnostic and prognostic biomarkers in a broad spectrum of cancers. In our present study, 12 lncRNAs identified from clinical samples from our erstwhile PCa patients were docked with PCa and AR targeted 36 proteins. We identified three lncRNAs, viz. SCARNA10, NPBWR1, ANKRD20A9P are common between the targeted proteins and discern that SCARNA10 lncRNA could serve as a prognostic signature for PCa and AR biogenesis. We also sought to check the coding potential of interfacial residues associated with lncRNA docking sites.x

bioinformatics↗

bioRxiv2023

Gut feeling: Extent of virulence and antibiotic resistance genes in Helicobacter pylori and campylobacteria

BackgroundHelicobacter pylori, a member of campylobacteria, is the leading cause of chronic gastritis and gastric cancer. Virulence and antibiotic resistance of H. pylori are of great concern to public health. However, the relationship between virulence and antibiotic resistance genes in H. pylori in relation to other campylobacteria remains unclear. Materials and MethodsBy using the virulence and comprehensive antibiotic resistance databases, we explored all available 354 complete genomes of H. pylori and compared it with 90 species of campylobacteria for virulence and antibiotic resistance genes/proteins. ResultsOn average, H. pylori had 129 virulence genes, highest among Helicobacter spp. and 71 antibiotic resistance genes, one of the lowest among campylobacteria. Just 2.6% of virulence genes were shared by all campylobacterial members, whereas 9.4% were unique to H. pylori. The cytotoxin-associated genes (cags) seemed to be exclusive to H. pylori. Majority of the isolates from Asia and South America were cag2-negative and many antibiotic resistance genes showed isolate-specific patterns of occurrence. Just 15 (8.8%) antibiotic resistance genes, but 103 (66%) virulence genes including 25 cags were proteomically identified in H. pylori. Arcobacterial members showed large variation in the number of antibiotic resistance genes and there was a positive relation with the genome size. ConclusionLarge repository of antibiotic resistance genes in campylobacteria and a unique set of virulence genes might have important implications in shaping the course of virulence and antibiotic resistance in H. pylori.

bioinformatics↗

bioRxiv2022

Integrative Multi-Omics Approaches for Identifying Cervical Cancer Therapeutic Targets

After breast cancer, cervical cancer (CC) is one of the most common malignancies in women globally. Over 90% of chronic infections are caused by human papillomavirus (HPV) and its subtypes. Extensive research efforts are required to identify the treatment targets and prognostic indicators for recurring and metastatic cancers. It may be possible because of omics methods, including genomes, epigenomics, transcriptomics, proteomics, and metabolomics. High throughput (HT) data on the differential mRNA and miRNA expression and their crucial interrelationships enable promising integration and interpretation of the results. Clinical data and multi-omics have risen to the top of the heap in delivering molecular and cellular activities. They aid in comparing data from different omics approaches and bridging the gap between genotype and phenotype. Therefore, multi-omic techniques may improve the knowledge of the molecular basis of the physiology and primary cause of disease, revealing a new route for the prognosis, diagnosis, prevention, and therapy of human diseases.

systems biology↗

bioRxiv2022

Tropical high-altitude insects show limited capacity to handle high temperatures

Growing summer season and increased anthropogenic activities pose a continual challenge to resident species. Ectotherms like insects are especially vulnerable to rapid climatic changes. High-altitude tropical insect populations have been rarely examined for their responses to high-temperature. We exposed a tropical out-bred highland population of Drosophila melanogaster from the Himalayas to growing summer conditions in outdoor mesocosm units. Population response to thermal changes was tracked over ninety days at both phenotypic and genotypic level. Whole genomic resequencing data suggested a clear seasonal shift in allele frequencies. Interestingly, the general heat responsive genes were missing in the summer due to monsoon allele shift; an atypical response noted for high-altitude tropical populations. Instead, candidates involved in kinases and phosphorylation emerged as key players. Heat-knockdown time decreased over time indicating a limited ability to handle increasing temperature. Merging data from both allelic shifts and heat-knockdown time indicated a limited capacity for high-altitude insects in coping with climate warming.

evolutionary biology↗

bioRxiv2022

Prevalence and heterogeneity of antibiotic-resistant genes in Orientia tsutsugamushi and other rickettsial genomes

Despite a million infections every year and an estimated one billion people at risk, scrub typhus is regarded as a neglected tropical disease. The causative bacterium Orientia tsutsugamushi, a member of rickettsiae, seems to be intrinsically resistant to several classes of antibiotics. The emergence of antibiotic-resistant scrub typhus is likely to become a global public health concern. Yet, it is unknown as to how common antibiotic-resistant genes are in O. tsutsugamushi, and how variable these loci are among the genomes of rickettsiae. By using the comprehensive antibiotic resistance database, we explored 79 complete genomes from 24 species of rickettsiae for putative antibiotic-resistant loci. There were 244 unique antibiotic-resistant genes in rickettsiae. Both the total and unique antibiotic-resistant genes in O. tsutsugamushi were significantly less compared to other members of rickettsiae. However, antibiotic-resistant genes in O. tsutsugamushi genomes were more unique and highly variable. Many genes such as resistant versions of evgS, and vanS A/G were present in numerous copies. These results will have important implications in the context of antibiotic-resistant scrub typhus.

bioinformatics↗

bioRxiv2019

A Simplest Bioinformatics Pipeline for Whole Transcriptome Sequencing: Overview of the Processing and Steps from Raw Data to Downstream Analysis.

Recent advances in next generation sequencing (NGS) technologies have heralded the genomic research. From the good-old inferring differentially expressed genes (DEG) using microarray to the current adage NGS-based whole transcriptome or RNA-Seq pipelines, there have been advances and improvements. With several bioinformatics pipelines for analysing RNA-Seq on rise, inferring the candidate DEGs prove to be a cumbersome approach as one may have to reach consensus among all the pipelines. To Check this, we have benchmarked the well known cufflinks-cuffdiff pipeline on a set of datasets and outline it in the form of a protocol where researchers interested in performing whole transcriptome shotgun sequencing and its downstream analysis can better disseminate the analysis using their datasets.

bioinformatics↗

bioRxiv2017

A Web-resource for Nutrient Use Efficiency related Genes, QTLs, and microRNA in important cereals and model plants

Cereals are the key contributors to global food security. Genes involved in uptake (transport), assimilation and utilization of macro- and micro-nutrients are responsible for their content in grain and straw. Although many cereal genomic databases are available, currently there is no cohesive web-resource of manually curated nutrient use efficiency (NtUE) related genes and QTLs, etc. In this study, we present a web-resource containing information on NtUE related genes/QTLs and the corresponding available microRNAs for some of these genes in four major cereal crops [wheat (Triticum aestivum), rice (Oryza sativa), maize (Zea mays), barley (Hordeum vulgare)], two alien species (Triticum urartu and Aegilops tauschii) related to wheat, and two model species including Brachypodium distachyon and Arabidopsis thaliana. Gene annotations integrated in the current web-resource were collected from the existing databases and the available literature. The primary goal of developing this web-resource is to provide descriptions of the NtUE related genes and their functional annotation. MicroRNA targeting some of the NtUE related genes and the quantitative trait loci (QTLs) for NtUE related traits are also included. The available information in the web-resource should help the users to readily search the desired information.\n\nWeb-resource URLhttp://bioclues.org/NtUE/

bioinformatics↗

bioRxiv2017

Genome-Wide Mining, Characterization and Development of miRNA-SSRs in Arabidopsis thaliana

Simple Sequence Repeats (SSRs), also known as microsatellites are short tandem repeats of DNA sequences that are 1-6 bp long. In plants, SSRs serve as a source of important class of molecular markers because of their hypervariabile and co-dominant nature, making them useful both for the genetic studies and marker-assisted breeding. The SSRs are widespread throughout the genome of an organism, so that a large number of SSR datasets are available, most of them from either protein-coding regions or untranslated regions. It is only recently, that their occurrence within microRNAs (miRNA) genes has received attention. As is widely known, miRNA themselves are a class of non-coding RNAs (ncRNAs) with varying length of 19-22 nucleotides (nts), which play an important role in regulating gene expression in plants under different biotic and abiotic stresses. In this communication, we describe the results of a study, where miRNA-SSRs in full length pre-miRNA sequences of Arabidopsis thaliana were mined. The sequences were retrieved by annotations available at EnsemblPlants using BatchPrimer3 server with miRNA-SSR flanking primers found to be well distributed. Our analysis shows that miRNA-SSRs are relatively rare in protein-coding regions but abundant in non-coding region. All the observed 147 di-, tri-, tetra-, penta- and hexanucleotide SSRs were located in non-coding regions of all the 5 chromosomes of A. thaliana. While we confirm that miRNA-SSRs were commonly spread across the full length pre-miRNAs, we envisage that such studies would allow us to identify newly discovered markers for breeding studies.

bioinformatics↗

bioRxiv2017

HYPO: A database of hypothetical human proteins

All annotated genes were once hypothetical or uncharacterized. Keeping this as an epilogue, we have enhanced our former database of hypothetical proteins (HP) in human (HypoDB) with added annotation, application programming interfaces and descriptive features. The database hosts 1000+ manually curated records of the known unknown regions in the human genome. The new updated version of HypoDB with functionalities (Blast, Match) is freely accessible at http://www.bioclues.org/hypo2.

bioinformatics↗

bioRxiv2017

A Bioinformatics Pipeline for Whole Exome Sequencing: Overview of the Processing and Steps from Raw Data to Downstream Analysis

Recent advances in next generation sequencing (NGS) technologies have given an impetus to find causality for rare genetic disorders. Since 2005 and aftermath of the human genome project, efforts have been made to understand the rare variants of genetic disorders. Benchmarking the bioinformatics pipeline for whole exome sequencing (WES) has always been a challenge. In this protocol, we discuss detailed steps from quality check to analysis of the variants using a WES pipeline comparing them with reposited public NGS data and survey different techniques, algorithms and software tools used during each step. We observed that variant calling performed on exome and whole genome datasets have different metrics generated when compared to variant callers, GATK and VarScan with different parameters. Furthermore, we found that VarScan with strict parameters could recover 80-85% of high quality GATK SNPs with decreased sensitivity from NGS data. We believe our protocol in the form of pipeline can be used by researchers interested in performing WES analysis for genetic diseases and by large any clinical phenotypes.

bioinformatics↗