Biology subjects

Amar, A.

Publications and source records attributed to Amar, A..

7 recordsLinked to original sources

bioRxiv2025

Identification of Novel Fusion Genes in Pediatric B-ALL patients Using Whole Transcriptome Sequencing

BackgroundFusion genes (FGs), serving as diagnostic, prognostic, and therapeutic markers, are key molecular aberrations in acute leukemia. They are also essential for risk stratification and measurable residual disease (MRD) monitoring. This study aimed to characterize the distribution of FGs using whole transcriptome sequencing (WTS). Materials and MethodsA total of 12 newly diagnosed treatment naive pediatric B-ALL cases from a local tertiary care hospital were enrolled in this study. Following the nucleic acids isolation procedures, the RNA sequencing was done for 12 B-ALL patients to find the fusion genes. ResultsIn the present cohort of 12 pediatric B-ALL patients, 19 high-confidence in-frame gene fusion events were identified involving 29 unique partner genes. The commonly reported sub-type defining rearrangements in B-ALL, including ETV6-RUNX1, TCF3-PBX1 and BCR-ABL1, were found in 8.3 % of the patients whereas the rearrangements in commonly prevalent genes in B-ALL like PAX5, ABL1 and ATXN3 were also found in 8.3 % of the patients with different unreported partner genes but reported earlier in various studies i.e. PAX-ETV6 (8.3%), ABL1-SNX2 (8.3%) and CMC2-ATXN3. ConclusionThe present work expands the scope of fusions in pediatric B-ALL by revealing unreported and domain-retaining fusions, as well as co-occurring rearranged fusions with possible combinatorial outcomes. By introducing WTS into clinical workflows, the genetic classification can be done more accurately and new pathogenic drivers missed by traditional methods can be identified, highlighting the increased significance of transcriptomic profiling in the diagnosis, prognosis, and personalized therapy of leukemia.

genomics↗

bioRxiv2025

Can In Silico Models Predict Drug-Induced Cardiac Risk in Vulnerable Populations?

This study evaluates virtual cardiac populations for preclinical assessment of drug-induced QT interval prolongation and arrhythmic risk. Traditional predictions often rely on small, healthy cohorts, excluding vulnerable populations. Using computational models of realistic heart anatomies and electrophysiology, we generated a virtual cohort of 512 subjects across healthy and diseased hearts (heart failure, dilated and hypertrophic cardiomyopathy, ischaemia, and myocardial infarction). We assessed QT prolongation and arrhythmic events following administration of moxifloxacin (benchmark antibiotic) and contraindicated drugs including quinidine, bepridil, and flecainide. Patients with heart failure, hypertrophic and dilated cardiomyopathy showed greater QT prolongation to moxifloxacin, unlike ischaemia and myocardial infarction, which resembled healthy subjects. Females exhibited consistently higher QT prolongation than males. Contraindicated drugs markedly increased arrhythmia risk in populations with heart failure, dilated and hypertrophic cardiomyopathy, and ischaemia, frequently leading to lethal arrhythmias such as Torsades des Pointes or ventricular fibrillation, particularly in females. These findings demonstrate that computational models capture variability in drug response across pathologies and sexes, offering a predictive framework for preclinical safety evaluations and supporting safer, more personalized drug development strategies.

bioengineering↗

bioRxiv2022

Causes, temporal trends and the effects of urbanisation on admissions of wild raptors to rehabilitation centres in England and Wales

Data from wildlife rehabilitation centres can provide on-the-ground records of causes of raptor morbidity and mortality, allowing threat patterns to be explored throughout time and space. We provide an overview of native raptor admissions to four wildlife rehabilitation centres (WRCs) in England and Wales, quantifying the main causes of morbidity and mortality, trends over time and whether certain causes were more common in more urbanised areas between 2001-2019. Throughout the study period 14 raptor species were admitted totalling 3305 admission records. The Common Buzzard (Buteo buteo; 31%) and Tawny Owl (Strix aluco; 29%) were most numerous. Relative to the proportion of breeding individuals in Britain & Ireland, Peregrine Falcons (Falco peregrinus), Little Owls (Athene noctua) and Western Barn Owls (Tyto alba) were over-represented in the admissions data by 103%, 73% and 69%, respectively. Contrastingly Northern Long-eared Owls (Asio otus), Western Marsh Harriers (Circus aeruginosus) and Merlin (Falco columbarius) were under-represented by 187%, 163% and 126%, respectively. Across all species, vehicle collisions were the most frequent anthropogenic admission cause (22%) and orphaned young birds (10%) were most frequent natural admission cause. Mortality rate was highest for infection/parasite admissions (90%), whereas orphaned birds experienced lowest mortality rates (16%). For one WRC, there was a notable decline in admissions over the study period. Red Kite (Milvus milvus) admissions increased over time, whereas Common Buzzard and Common Kestrel admissions declined. There were significant declines in the relative proportion of persecution and metabolic admissions, and an increase in orphaned young birds. Urban areas were positively associated with persecution, building collisions and unknown trauma admissions, whereas vehicle collisions were associated with more rural areas. Many threats persist for raptors in England and Wales, however, have not changed substantially over the past two decades. Threats associated with urban areas, such as building collisions, may increase over time in line with human population growth and subsequent urban expansion.

ecology↗

bioRxiv2021

Modeling the C. elegans Germline Stem Cell Genetic Network using Automated Reasoning

Computational methods and tools are a powerful complementary approach to experimental work for studying regulatory interactions in living cells and systems. We demonstrate the use of formal reasoning methods as applied to the Caenorhabditis elegans germ line, which is an accessible model system for stem cell research. The dynamics of the underlying genetic networks and their potential regulatory interactions are key for understanding mechanisms that control cellular decision-making between stem cells and differentiation. We model the "stem cell fate" versus entry into the "meiotic development" pathway decision circuit in the young adult germ line based on an extensive study of published experimental data and known/hypothesized genetic interactions. We apply a formal reasoning framework to derive predictive networks for control of differentiation. Using this approach we simultaneously specify many possible scenarios and experiments together with potential genetic interactions, and synthesize genetic networks consistent with all encoded experimental observations. In silico analysis of knock-down and overexpression experiments within our model recapitulate published phenotypes of mutant animals and can be applied to make predictions on cellular decision-making. This work lays a foundation for developing realistic whole tissue models of the C. elegans germ line where each cell in the model will execute a synthesized genetic network.

systems biology↗

bioRxiv2020

The AMPK-related kinase NUAK1 controls cortical axons branching though a local modulation of mitochondrial metabolic functions

The precise regulation of the cellular mechanisms underlying axonal morphogenesis is essential to the formation of functional neuronal networks. We previously identified the autism-candidate kinase NUAK1 as a central regulator of axon branching in mouse cortical neurons through the control of mitochondria trafficking. How does local mitochondrial position or function regulate axon branching during development? Here, we characterized the metabolic regulation in the developing axon and report a marked metabolic decorrelation between axon elongation and collateral branching. We next solved the cascade of event leading to presynaptic clustering and mitochondria recruitment during spontaneous branch formation. Interestingly and contrary to peripheral neurons, mitochondria are recruited after but not prior to branch formation in cortical neurons. Using flux metabolomics and fluorescent biosensors, we observed that NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration. Upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Altogether, our results indicate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondria distribution and activity, and suggest that a mitochondrial-dependent remodeling of local metabolic homeostasis plays a critical role during axon morphogenesis.

neuroscience↗

bioRxiv2018

Streptococcus salivarius - a potential salivary biomarker for orofacial granulomatosis and Crohn’s disease?

ObjectiveOrofacial granulomatosis (OFG) is a rare disease characterised by chronic, non-caseating, granulomatous inflammation primarily affecting the oral cavity. Histologically, it is similar to Crohns disease (CD) and a proportion of patients have both OFG and CD. The cause of OFG remains elusive but it has been suggested that microbial interactions may be involved. The aim of this study was to compare the salivary microbial composition of subjects with OFG and/or CD and healthy controls.\n\nDesign261 subjects were recruited, of whom 78 had OFG only, 40 had both OFG and CD, 97 had CD only with no oral symptoms and 46 were healthy controls. Bacterial community profiles were obtained by sequencing the V1-V3 region of the 16S rRNA gene.\n\nResultsThere were no differences in richness or diversity of the salivary bacterial communities between patient groups and controls. The relative abundance of the Streptococcus salivarius-group were raised in patients with OFG or CD only compared to controls while that of the Streptococcus mitis -group was lower in CD compared to both OFG and controls. One S. salivarius oligotype made the major contribution to the increased proportions seen in patients with OFG and CD.\n\nConclusionThe salivary microbiome of individuals with OFG and CD was similar to that found in health although the proportions of S. salivarius, a common oral Streptococcus were raised. One specific strain-level oligotype was found to be primarily responsible for the increased levels seen.

microbiology↗

bioRxiv2017

Exome sequencing and genotyping identify a rare variant in NLRP7 gene associated with ulcerative colitis.

Background and aimsAlthough genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) have identified a large number of common disease susceptibility alleles for both Crohns disease (CD) and ulcerative colitis (UC), a substantial fraction of IBD heritability remains unexplained, suggesting that rare coding genetic variants may also have a role in pathogenesis. We used high-throughput sequencing in families with multiple cases of IBD, followed by genotyping of cases and controls, to investigate whether rare protein altering genetic variants are associated with susceptibility to IBD.\n\nMethodsWhole exome sequencing was carried out in 10 families in which 3 or more individuals were affected with IBD. A stepwise filtering approach was applied to exome variants to identify potential causal variants. Follow-up genotyping was performed in 6,025 IBD cases (2,948 CD; 3,077 UC) and 7,238 controls.\n\nResultsOur exome variant analysis revealed coding variants in the NLRP7 gene that were present in affected individuals in two distinct families. Genotyping of the two variants, p.S361L and p.R801H, in IBD cases and controls showed that the p.S361L variant was significantly associated with an increased risk of ulcerative colitis (odds ratio 4.79, p=0.0039) and IBD (odds ratio 3.17, p=0.037). A combined analysis of both variants showed suggestive association with an increased risk of IBD (odds ratio 2.77, p=0.018).\n\nConclusionsThe results suggest that NLRP7 signalling and inflammasome formation may be a significant component in the pathogenesis of IBD.

genetics↗