Biology subjects

Saini, S.

Publications and source records attributed to Saini, S..

47 records · Page 3Linked to original sources

bioRxiv2020

TRTools: a toolkit for genome-wide analysis of tandem repeats

SummaryA rich set of tools have recently been developed for performing genome-wide genotyping of tandem repeats (TRs). However, standardized tools for downstream analysis of these results are lacking. To facilitate TR analysis applications, we present TRTools, a Python library and a suite of command-line tools for filtering, merging, and quality control of TR genotype files. TRTools utilizes an internal harmonization module making it compatible with outputs from a wide range of TR genotypers. AvailabilityTRTools is freely available at https://github.com/gymreklab/TRTools. Contactmgymrek@eng.ucsd.edu Supplementary informationSupplementary data are available at bioRxiv.

bioinformatics↗

bioRxiv2019

DAVI:Deep Learning Based Tool for Alignment and Single Nucleotide Variant identification

The Next Generation Sequencing (NGS) technologies have provided affordable ways to generate errorful raw genetical data. To extract Variant Information from billions of NGS reads is still a daunting task which involves various hand-crafted and parameterized statistical tools. Here we propose a Deep Neural Networks (DNN) based alignment and SNV tool known as DAVI. DAVI consists of models for both global and local alignment and for Variant Calling. We have evaluated the performance of DAVI against existing state of the art tool-set and found that its accuracy and performance is comparable to existing tools used for benchmarking. We further demonstrate that while existing tools are based on data generated from a specific sequencing technology, the models proposed in DAVI are generic and can be used across different NGS technologies. Moreover, this approach is a migration from expert driven statistical models to generic, automated, self-learning models.

bioinformatics↗

bioRxiv2018

Multi-tissue analysis reveals short tandem repeats as ubiquitous regulators of gene expression and complex traits

Short tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and provide insights into putative mechanisms. Here, we leverage whole genome sequencing and expression data for 17 tissues from the Genotype-Tissue Expression Project (GTEx) to identify STRs for which repeat number is associated with expression of nearby genes (eSTRs). Our analysis reveals more than 28,000 eSTRs. We employ fine-mapping to quantify the probability that each eSTR is causal and characterize a group of the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published GWAS signals and implicate specific eSTRs in complex traits including height and schizophrenia, inflammatory bowel disease, and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes and will serve as a valuable resource for future studies of complex traits.

genomics↗

bioRxiv2018

Nucl2Vec: Local alignment of DNA sequences using Distributed Vector Representation

The Next Generation Sequencing Technique (NGS) has provided affordable and fast method for generating genetic data. Generation of whole Genome Sequence and extract relevant information from this data is still a computationally expensive process. In this paper we demonstrate a novel approach for local alignment of DNA reads with respect to reference genome. For this process we have used Skip-gram model for creating encoding(Nucl2Vec) and k-nearest neighbor for the alignment. With our new approach we have reduced computation cost for local alignment, while achieving accuracy comparable to existing defacto standard BWA-MEM tool.\n\nIndex TermsGenome, Alignment, Local Alignment, k-nearest Neighbor, Distributed vector representation, Skip-gram

genomics↗

bioRxiv2018

SHORT TERM EVOLUTIONARY DYNAMICS OF ESCHERICHIA COLI IN DIFFERENT CARBON ENVIRONMENTS

Starting from a parentalE. coli K-12 MG1655 strain, we evolve cells in five different carbon environments-glucose, arabinose, xylose, rhamnose, and a mixture of these four sugars (in a predefined ratio) for approximately 2,000 generations. At the end of the adaptation period, we quantify and compare growth dynamics of the strains in a variety of environments. The evolved strains show no specialized adaptation towards growth in the carbon medium in which they were evolved. Rather, in all environments, the evolved strains exhibited a reduced lag phase and an increased growth rate. Sequencing results reveal that these dynamical properties are not introduced via mutations in the precise loci associated with utilization of the sugar in which the bacterium was evolved in. These phenotypic changes are rather likely introduced via mutationselsewhere onthe genome. Sugar systems are known to exhibit hierarchy in utilization. Evolution in a defined environment, in our experimental framework, does not alter this hierarchy.

microbiology↗

bioRxiv2018

DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169

Human DYRK1A gene encoding Dual-specificity tyrosine (Y)- Regulated Kinase 1A (DYRK1A) is a dosage-dependent gene whereby either trisomy or haploinsufficiency result in developmental abnormalities. However, the function and regulation of this important protein kinase are not fully understood. Here we report proteomic analysis of DYRK1A in human cells that revealed a novel role of DYRK1A in the DNA double-strand break (DSB) repair signaling. This novel function of DYRK1A is mediated in part by its interaction with ubiquitin-binding protein RNF169 that regulates the choice between homologous recombination (HR) and non-homologous end joining (NHEJ) DSB repair. Accumulation of RNF169 at the DSB sites promotes homologous recombination (HR) by limiting the recruitment of the scaffold protein 53BP1 that promotes NHEJ by protecting the DNA ends from resection. Inducible overexpression of active, but not the kinase inactive, DYRK1A in U-2 OS cells inhibited accumulation of 53BP1 at the DSB sites in RNF169-dependent manner. Mutation of DYRK1A phosphorylation sites in RNF169 or pharmacological inhibition of DYRK1A using harmine decreased the ability of RNF169 to displace 53BP1 from radiation-induced DSB sites. In order to further investigate the role of DYRK1A in regulation of DNA repair, we used CRISPR-Cas9 mediated knockout of DYRK1A in human and mouse cells. Interestingly, knockout of DYRK1A also caused a defect in 53BP1 DSB recruitment that was independent of RNF169, suggesting that dosage of DYRK1A can influence the DNA repair processes through several mechanisms. U-2 OS cells devoid of DYRK1A displayed an increased DNA repair and HR efficiency, and showed a decreased sensitivity to the PARP inhibitor olaparib when compared to control cells. Given evidence of its altered expression in human cancers, DYRK1A levels could represent a significant determinant of the DNA damaging therapy response.

molecular biology↗

bioRxiv2018

Estimating Optimal Lysogenic Propensity for Viruses in Stressed Environments

Abstract.Having infected a bacterial cell, a temperate phage has to make a choice between (a) integrating itself into the bacterial genome, i.e. lysogeny, and (b) using the bacterial machinery to create multiple copies of itself and lysing the cell in the process, i.e. lysis. In order to maximize its long-term growth rate, phages need to ensure that they do not wipe off their bacterial hosts. Temperate phages have been observed to exhibit lysogenic propensities dependent on the MoI (Multiplicity of Infection), among other factors. We propose a model to estimate the propensity of lysogeny opted for by the phages in order to maximize coexistence. One possible approach to do so is to adopt a strategy that would help to attain and maintain an approximately equal proportion of phages with respect to their host. We find that the optimal fraction of phages opting for lysogeny follows a sigmoidal relationship with the MoI and is comparable to results obtained experimentally. We further assess the impact of phage and bacterial environmental stresses on the lysogenic propensity. Our results indicate that the optimal value of lysogenic propensity is greatly dependent on the intensity of these stresses.

systems biology↗

bioRxiv2018

A reference haplotype panel for genome-wide imputation of short tandem repeats

Short tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in a variety of complex traits. However, existing technologies focusing on single nucleotide polymorphisms (SNPs) have not allowed for systematic STR association studies. Here, we leverage next-generation sequencing data from 479 families to create a SNP+STR reference haplotype panel for genome-wide imputation of STRs into SNP data. Imputation achieved an average of 97% concordance between genotyped and imputed STR genotypes in an external dataset compared to 63% expected under a random model. Performance varied widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic forensics markers. We demonstrate that imputation increases power over individual SNPs to detect STR associations using simulated phenotypes and gene expression data. This resource will enable the first large-scale STR association studies using existing SNP datasets, and will likely yield new insights into complex traits.

genomics↗

bioRxiv2018

Mathematical Modelling of Actin treadmill in Apicomplexans

Plasmodium parasite, a representative member of phylum Apicomplexa is a causative agent of malaria in human as well as other animals. To infect host cells, Plasmodium first finds receptors on the host cell surface, then binds specifically, and finally penetrates host cell membrane to acquire the host cellular resources. The motility for moving on the cell surface is equipped by the precise and tight control of actin treadmill. Several regulators are required to achieve precision and robustness in the control of actin treadmill. However, the mechanistic detail of the treadmill regulatory network and the cross-talk among regulators are not well understood. We developed a stochastic model of treadmill regulation and explored the dynamics of filament growth, nucleation time, and elongation time. Our study mainly highlighted on how and what helps cells to maintain an average size of the actin filaments within a species. This is particularly important, since, excessive growth of filament can lead to cell lysis. Moreover, we also explore how the regulators interact to fine-tune the control elements in the actin treadmill.

systems biology↗

bioRxiv2017

Rob And MarA Alter Susceptibility Of Escherichia coli To Antibiotics In Presence Of Salicylate

When exposed to stress, bacterial cells launch a diverse response to enhance their chances of survival. This response involves modulation of expression of a large number of proteins which help the cell counter stress. This modulation is facilitated by several transcription factors in bacteria and in E. coli three homologous regulators, MarA, Sox, and Rob are known to launch a coordinated response to combat various stress environments. MarA and SoxS are known to control multiple antibiotic resistance and superoxide regulon respectively. Rob has been observed to control similar downstream targets as MarA and SoxS. However, physiological relevance of Rob in not understood. We show that Rob along with MarA, in presence of inducer salicylate, can help cell survive in presence of lethal concentration of wide range of antibiotics.

microbiology↗

bioRxiv2016

Genome Wide Computational Prediction of miRNAs in Kyasanur Forest Disease Virus and their Targeted Genes in Human

RNAs are versatile biomolecules and can be coding or non-coding. Among the non-coding RNAs, miRNAs are small endogenous molecules that play important role in posttranscriptional gene regulation. miRNAs are identified in viruses too and involved in down regulation of host genes. Flavivirus family members are classified in to two groups: mosquito-borne flaviviruses (MBFV) and tick-borne flaviviruses (TBFV). Kyasanur forest disease virus (KFDV) found in India in 1957 (Karnataka) relates to TBFV. Virus has been diffuse to new areas in India and needs attention as it can cause severe hemorrhagic fever. Here in this study, we scanned the virus genome for prediction of miRNAs that can inhibit host target genes. VMir, tool was used for extraction of pre-miRNAs. A total of four miRNAs were found and submitted to ViralMir for classification in to real or pseudo. Interestingly, all four pre-miRNAs were classified as real. Eight mature miRNAs were located in pre-miRNAs by Mature Bayes. A total of 539 human target genes has been identified by using miRDB but ANGPT1 (angiopoietin 1) and TFRC (transferrin receptor) genes were screened to play role in hemorrhagic fever and neurological problems. GO analysis of target genes also supported the evidences.

bioinformatics↗