Biology subjects

Hasan, S.

Publications and source records attributed to Hasan, S..

25 records · Page 2Linked to original sources

bioRxiv2020

Genome Analysis of SARS-CoV-2 Isolate from Bangladesh

Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.

genomics↗

bioRxiv2020

Aberrant synaptic release underlies sleep/wake transition deficits in a mouse Vamp2 mutant

Sleep-wake transitions are modulated through extensive subcortical networks although the precise roles of their individual components remain elusive. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterised by a reduced propensity to transition between all sleep states while a profound loss in total REM sleep time was evident. The causative mutation, an Ile102Asn substitution in VAMP2, was associated with substantial synaptic changes while in vitro electrophysiological investigations with fluorescence imaging revealed a diminished probability of vesicular release in mutants. We conclude that the synaptic efficiency of the entire subcortical brain network determines the likelihood that an animal transitions from one vigilance state to the next.

neuroscience↗

bioRxiv2019

The NAD+-dependent deacetylase Sir2 enables evolution of new traits by regulating distinct gene sets in two yeast species, Saccharomyces cerevisiae and Kluyveromyces lactis

Evolutionary adaptation increases the fitness of an organism in its environment. It can occur through rewiring of gene regulatory networks, such that an organism responds appropriately to environmental changes. We investigated whether sirtuin deacetylases, which repress transcription and require NAD+ for activity, could facilitate the evolution of potentially adaptive responses by serving as transcriptional rewiring points. If so, bringing genes under the control of sirtuins could enable organisms to mount appropriate responses to stresses that decrease NAD+ levels. To explore how the genomic targets of sirtuins shift over evolutionary time, we compared two yeast species, Saccharomyces cerevisiae and Kluyveromyces lactis that display differences in cellular metabolism and lifecycle timing in response to nutrient availability. We identified sirtuin-regulated genes through a combination of chromatin immunoprecipitation and RNA expression. In both species, regulated genes were associated with NAD+ homeostasis, mating, and sporulation, but the specific genes differed. In addition, regulated genes in K. lactis were associated with other processes, including utilization of non-glucose carbon sources, heavy metal efflux, DNA synthesis, and production of the siderophore pulcherrimin. Consistent with the species-restricted regulation of these genes, sirtuin deletion impacted relevant phenotypes in K. lactis but not S. cerevisiae. Finally, sirtuin-regulated gene sets were depleted for broadly-conserved genes, consistent with sirtuins regulating processes restricted to a few species. Taken together, these results are consistent with the notion that sirtuins serve as rewiring points that allow species to evolve distinct responses to low NAD+ stress.

evolutionary biology↗

bioRxiv2019

Profiling Gene Specific Changes to RNA Editome in Preeclampsia

RNA editing is a form of post-transcriptional modification that results in changes to the messenger RNA sequence. At the onset of the study we focused on detecting the changes in RNA editing patterns in cell lines exposed to hypoxic conditions followed by the detection of changes in RNA editing patterns in the fetuses of preeclamptic mothers using publicly available RNA sequence data from the NCBI SRA database. The results showed an increase in RNA editing activity in hypoxic cell lines and a decrease in RNA editing activity in the fetuses with preeclamptic mothers. A total of 85 genes common in the cell lines and 33 in the fetus disease models and not present in controls were identified as harboring editing sites in exonic, downstream, upstream or splicing regions. Subsequently we focused on unique editing sites in genes and categorized in order of relevance to Preeclampsia as A, B and C (A being most closely related to the disease and C the least). The genes implicated ones involved in respiration chains, blood cell growth, cytokine and complement activation. Among the most significant of the genes were CTSB, GSR, CASP10, and MAPK13. Total number of common editing sites were found in different conditions and these were 667 for cell lines and 23 for fetuses. Validation of these variations in a larger samples size determines refined editing sites which could be used as potential diagnostic markers for intervention.

genomics↗

bioRxiv2018

Differentiating Genomic SNPs Using Allele Depth and Predicted Genotype

Differentiating between genomic SNPs and other types of single nucleotide variants becomes a key issue in research aimed at studying the importance of these variants of a particular type in biological processes. Here we present an R based method for differentiating between genomic single nucleotide polymorphisms (SNPs) and RNA editing sites. We use data from an earlier study of ours and target only the known dbsnp SNPs that we found in our study. Our method involves calculating the ratio of allele depth for ref and alt alleles and comparing that to the predicted genotype. We use the concept that editing levels should be different for each allele and thus should not reflect the ratio predicted by the genotype. The study yielded an accuracy rate ranging from 86 to over 90 percent at successfully predicted dbsnp entries as SNPs. Albeit this is in the absence of known RNA editing site vcf data to compare as a reference.

genomics↗

bioRxiv2018

Identifying Changes in RNA Editome Unique to Major Depressive Disorder

Major Depressive Disorder (MDD) is one of the most significant psychiatric disorders in the world today. Its incidence is widespread in society and its heavy adverse impact on the quality of life is well documented. Previously genetic studies on MDD had identified a hereditary component of the disease as well as crediting RNA editing with a role in its development. The later due to an overexpression of a heavily edited isoform of the Serotonin 2c receptor. Here we used publicly available RNA sequence data from suicide patients diagnosed with MDD as well as controls for identifying RNA editing sites unique to MDD. After variant calling and several steps of filtering, we identified 142 unique RNA editing sites in the MDD patients. These included intronic, downstream, UTR3 and exonic edits. The latter comprising several amino acid changes in the encoded protein. The genes implicated to be uniquely edited in MDD included the aforementioned and previously implicated Serotonin 2c receptor, others involved in functions that play roles in depression and suicide such as Cannabinoid Receptor 1, Frizzled Class 3 Receptor, Neuroligin 3 and others.

genomics↗

bioRxiv2017

Designing an intuitive web application for drug discovery scientists

Although a scientific web application that is intuitive can help scientists utilize data more easily and advance their research, there is little guidance on how to design such an application in the academic literature. We discuss how we designed an intuitive application for bench scientists working in drug discovery following an approach that can be applied to the design and development of scientific resources in a broad range of disciplines.

bioinformatics↗