Biology subjects

Ahmed, S. S.

Publications and source records attributed to Ahmed, S. S..

12 recordsLinked to original sources

bioRxiv2025

Unfolded to Folded: Unraveling the Secrets of Protein Folding with ProteusFold

Protein folding has long been regarded as the "holy grail" of biology, typically demanding large models and massive GPU clusters. This study introduces Pro-teusFold, a compact and interpretable model with only 993,408 parameters that achieves state-of-the-art accuracy on modest hardware with an inference time of 0.0011 seconds. By framing folding as an unfolded-to-folded sequence transformation using a novel structural tokenization, ProteusFold reduces regression complexity while preserving bond connectivity through the concept of "Synapses." It achieves near-atomic fidelity (RMSD 0.24,[A], GDT-TS 99.85) and excels in protein-protein docking with a mean DockQ of 0.7675, with 95.5% of complexes above the 0.23 threshold. Compared to AlphaFold2s Predicted Aligned Error (6.28), ProteusFold attains 0.396, representing an order-of-magnitude gain in positional accuracy. Beyond accuracy and efficiency, the model provides residue-level attribution analyses that highlight biologically significant residues, serving as a preliminary guide for experiments. Furthermore, ProteusFold is the first to provide atomic-level attribution of key electronic and thermal properties, offering deeper insight into folding mechanisms and pinpointing the specific atoms responsible for distinct scenarios. Moreover, a meta-analysis suggests the presence of folding hotspots, where critical residues cluster, revealing new avenues for discovery. Thus, ProteusFold delivers accuracy, interpretability, and efficiency, broadening access to protein-folding research.

molecular biology↗

bioRxiv2024

Monoclonal antibodies targeting the FimH adhesin protect against uropathogenic E. coli UTI

As antimicrobial resistance increases, urinary tract infections (UTIs) are expected to pose an increased burden in morbidity and expense on the healthcare system, increasing the need for alternative antibiotic-sparing treatments. Most UTIs are caused by uropathogenic Escherichia coli (UPEC), while Klebsiella pneumoniae causes a significant portion of non-UPEC UTIs. Both bacteria express type 1 pili tipped with the mannose-binding FimH adhesin critical for UTI pathogenesis. We generated and biochemically characterized 33 murine monoclonal antibodies (mAbs) to FimH. Two mAbs protected mice from E. coli UTI. Mechanistically, we show that this protection is Fc-independent and mediated by the ability of these mAbs to sterically block FimH function. Our data reveals that FimH mAbs hold promise as an antibiotic-sparing treatment strategy.

microbiology↗

bioRxiv2023

Microbial Remediation of Pesticide Accumulation and its Response on Bacterial Wilt of Brinjal

Growing brinjal (Solanum melongena L.) in a soil polluted with organophosphorus pesticide (OP) residues coupled with an additional threat of wilt disease caused by Ralstonia solanacearum (Rs), pose a formidable management challenge for residue free crop production. Our study aimed at identifying efficient OP-degrading bacteria (OPDB) and their compatibility with microbial bio-control agents (MBCA) for twin objective of microbial degradation of OP -residues and reduction in incidence of bacterial wilt of brinjal in OP-contaminated soil. As many, ten bacterial isolates showing OP-degrading potential were recovered through colony growth in mineral salt (MS) - medium treated with 25 ppm chlorpyriphos. Efficient isolates displaying growth up to 700ppm chlorpyriphos were further screened for OP-degradation, leading to identification of two most efficient OPDB, Acromobacter marplatensis [MW397524] (Am) and Pseudomonas azotoformans [MW397525] (Pa). These two isolates having in vitro compatibility with each other, showed further compatibility with two most widely used MBCA, viz., Pseudomonas flourescens [KT258013] (Pf) and Trichoderma harzianum [ON364138] (Th), facilitating the development of consortium having extended functional corridor. The response of combination of OPDB + MBCA(Am +Pa + Pf + Th) showed 80% lower percent wilt incidence (PWI), 2.8 times higher fruit yield of brinjal, and 15-25% lower OP-residues over un-inoculated control treatment. Our studies, hence, put forward a strong unified delivery mechanism of OPDB and MBCA as a part of green technology for chemical residue -free vegetable production in contaminated soils. IMPORTANCEMicrobes isolated from crop rhizospheres are known to exhibit multiple functions (plant growth promotion, antagonism against soil borne pathogens e.g., Rs, and acaricidal properties) depending upon type of stimuli by regulating the plant defense. Considering the limited past efforts on twin objective of cleaning up the pesticide residues accumulated in the soil (microbial removal of pesticide residues) and providing an additional safeguard against soil borne pathogen causing bacterial wilt in brinjal to collectively develop a microbial consortia mediated crop production system, devoid of any chemical residues. Such an effort adds strength to organic production system on pesticide contaminated soils. In the present study, we succeeded in identifying two most effective chloropyrifos residues degrading OPDB having compatibility two MBCA for developing consortia formulation, which aided in developing pesticide residue free soil, neutralising bacterial wilt pathogen (Rs), and creating a better nutrient supply for a well deserved production system. Such efforts would pave the way for developing more robust microbial formulations (with emphasis on entomopathogenic application) having dynamic microbial functions to replace any futuristic use of agrochemcials.

microbiology↗

bioRxiv2022

The Ebola virus VP40 matrix undergoes endosomal disassembly essential for membrane fusion

Ebola viruses (EBOVs) are filamentous particles, whose shape and stability are determined by the VP40 matrix. Virus entry into host cells occurs via membrane fusion in late endosomes; however, the mechanism of how the remarkably long virions undergo uncoating including virion disassembly and nucleocapsid release into the cytosol, remains unknown. Here, we investigate the structural architecture of EBOVs entering host cells and discover that the VP40 matrix disassembles prior to membrane fusion. We reveal that VP40 disassembly is caused by the weakening of VP40-lipid interactions driven by low endosomal pH that equilibrates passively across the viral envelope without a dedicated ion channel. We further show that viral membrane fusion depends on VP40 matrix integrity, and its disassembly reduces the energy barrier for fusion stalk formation. Thus, pH-driven structural remodeling of the VP40 matrix acts as a molecular switch coupling viral matrix uncoating to membrane fusion during EBOV entry.

microbiology↗

bioRxiv2022

Duet: SNP-Assisted Structural Variant Calling and Phasing Using Oxford Nanopore Sequencing

BackgroundWhole genome sequencing (WGS) using the long-read Oxford Nanopore Technologies (ONT) MinION sequencer provides a cost-effective option for structural variant (SV) detection in clinical applications. Despite the advantage of using long reads, however, accurate SV calling and phasing are still challenging. ResultsWe introduce Duet, an SV detection tool optimized for SV calling and phasing using ONT data. The tool uses novel features integrated from both SV signatures and single-nucleotide polymorphism (SNP) signatures, which can accurately distinguish SV haplotype from a false signal. Duet was benchmarked against state-of-the-art tools on multiple ONT sequencing datasets of sequencing coverage ranging from 8X to 40X. At low sequencing coverage of 8X, Duet performs better than all other tools in SV calling, SV genotyping and SV phasing. When the sequencing coverage is higher (20X to 40X), the F1-score for SV phasing is further improved in comparison to the performance of other tools, while its performance of SV genotyping and SV calling remains comparable or higher than other tools. ConclusionDuet can perform accurate SV calling, SV genotyping and SV phasing using low-coverage ONT data, making it very useful for low-coverage genomes. It has great performance when scaled to high-coverage genomes, which is adaptable to various clinical applications. Duet is open source and is available at https://github.com/yekaizhou/duet.

bioinformatics↗

bioRxiv2022

Succinylated lysine residue prediction revisited

MotivationLysine succinylation is a kind of post-translational modification (PTM) which plays a crucial role in regulating the cellular processes. Aberrant succinylation may cause inflammation, cancers, metabolism diseases and nervous system diseases. The experimental methods to detect succinylation sites are time-consuming and costly. This thus calls for computational models with high efficacy and attention has been given in the literature for developing such models, albeit with only moderate success in the context of different evaluation metrics. One important aspect in this context is the biochemical and physicochemical properties of amino acids, which appear to be useful as features for such computational predictors. However, some of the existing computational models did not use the biochemical and physicochemical properties of amino acids, while some others used them without considering the inter-dependency among the properties. ResultsThe combinations of biochemical and physicochemical properties derived through our optimization process achieve better results than the results achieved by the combination of all the properties. We propose three deep learning architectures, CNN+Bi-LSTM (CBL), Bi-LSTM+CNN (BLC) and their combination (CBL_BLC). We find that CBL_BLC is outperforming the other two. Ensembling of different models successfully improves the results. Notably, tuning the threshold of the ensemble classifiers further improves the results. Upon comparing our work with other existing works on two datasets, we find that we successfully achieve better sensitivity and specificity through varying the threshold value. Availabilityhttps://github.com/Dariwala/Succinylation-with-biophysico-and-deep-learning Contactmsrahman@cse.buet.ac.bd

bioinformatics↗

bioRxiv2022

Clair3-Trio: high-performance Nanopore long-read variant calling in family trios with Trio-to-Trio deep neural networks

Accurate identification of genetic variants from family child-mother-father trio sequencing data is important in genomics. However, state-of-the-art approaches treat variant calling from trios as three independent tasks, which limits their calling accuracy for Nanopore long-read sequencing data. For better trio variant calling, we introduce Clair3-Trio, the first variant caller tailored for family trio data from Nanopore long-reads. Clair3-Trio employs a Trio-to-Trio deep neural network model, which allows it to input the trio sequencing information and output all of the trios predicted variants within a single model to improve variant calling. We also present MCVLoss, a novel loss function tailor-made for variant calling in trios, leveraging the explicit encoding of the Mendelian inheritance. Clair3-Trio showed comprehensive improvement in experiments. It predicted far fewer Mendelian inheritance violation variations than current state-of-the-art methods. We also demonstrated that our Trio-to-Trio model is more accurate than competing architectures. Clair3-Trio is accessible as a free, open-source project at https://github.com/HKU-BAL/Clair3-Trio.

bioinformatics↗

bioRxiv2021

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment

Not all cancer patients with severe neutropenia develop fever, and the fecal microbiome may play a role. In neutropenic hematopoietic cell transplant patients (n=119), 63 (53%) developed a subsequent fever and had increased fecal Akkermansia muciniphila, a mucus-degrading bacteria (p=0.006, corrected for multiple comparisons). In mouse models, two therapies, irradiation and melphalan, similarly expanded A. muciniphila. Dietary restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Azithromycin treatment depleted A. muciniphila and preserved colonic mucus. Dietary restriction raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila with lower pH and increased propionate prevented utilization of mucin. Treating irradiated mice with azithromycin or propionate preserved the mucus layer, lessened hypothermia, and reduced inflammatory cytokines in the colon. These results suggest that diet, metabolites and colonic mucus link the microbiome to neutropenic fever, and could guide future microbiome-based preventive strategies.

microbiology↗

bioRxiv2019

Insights into protein structural, physicochemical, and functional consequences of missense variants in 1,330 disease-associated human genes

Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variants on protein structure and function being especially challenging. Here we evaluated the burden of amino acids affected in pathogenic variants (n=32,923) compared to the variants (n=164,915) from the general population in 1,330 disease-associated genes on forty protein features using over 14,000 experimentally-solved 3D structures. By analyzing the whole gene/variant set jointly, we identified 18 features associated with 3D mutational hotspots that are generally important for protein fitness and stability. Individual analyses performed for twenty-four protein functional classes further revealed 240 characteristics of mutational hotspots in total, including new associations recapitulating the sheer diversity across proteins essential structural regions. We demonstrated that the function-specific features of variants correspond to the readouts of mutagenesis experiments and positively correlate with clinically-interpreted pathogenic and benign missense variants. Finally, we made our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step towards translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the pathogenicity of variants in terms of the perturbed molecular mechanisms.

genetics↗

bioRxiv2018

Translationally Controlled Tumor Protein TCTP as Peptide Vaccine against Schistosoma japonicum: an Immunoinformatics Approach

Schistosoma japonicum is the most pathogenic causative form of schistosomiasis that causes a major health problem in its endemic countries. Until now, praziquantel is the only drug used to treat Schistosomiasis, but it does not prevent re-infection. So, repetition of the treatment is needed. Moreover, there is no effective vaccine against S. japonicum. Therefore, an urgent need for the development of vaccines is mandatory. This study aimed to analyze an immunogenic protein, Transitionally Controlled Tumor Protein (TCTP) using an immunoinformatics approach to design a universal peptide vaccine against Schistosoma japonicum. A set of 22 of TCTP sequences were retrieved from NCBI database. Conservancy of these sequences was tested and then conserved B cell and T cell epitopes were predicted using different tools available in IEBD. Epitopes having high scores in both B and T cell predicting tools were proposed. An epitope 129YEHYI133 was predicted as a most promising epitope with good prediction scores in surface accessibility and antigenicity. Besides that, epitopes 129YEHYIGESM 137and 92YLKAIKERL100 were predicted as the most promising epitopes concerning their binding to MHC I and MHC II allele respectively. The study revealed that our predicted epitopes could be used to develop an efficacious vaccine against Schistosoma japonicum in the future especially epitope YEHYIGESM as it is shared between MHC I and II alleles and overlapped with the most promising B cell epitope. Both in vitro and in vivo studies is recommended to confirm the efficacy of YEHYIGESM as a peptide vaccine.

bioinformatics↗

bioRxiv2018

Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins

Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5 and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P=0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.

microbiology↗

bioRxiv2018

Ameliorative potential of curcumin on cigarette smoke extract induced cognitive impairment in zebrafish

Curcumin is a major phyto-constituent of Curcuma longa. It has been reported that it that it showed various pharmacological actions via anti-oxidant, anti-inflammatory, and immunomodulatory actions. The present study undergoes the therapeutic evaluation of curcumin in cigarette smoke extract (CSE) exposure induced cognitive impairment in zebrafish. Methods: The cognitive impairment was induced by exposure to 25 ml of 200 % CSE; 10 minutes/day, for 7 consecutive days. The pre-treatment of curcumin (10 and 20 mg/kg) and montelukast(20 mg/kg) were exposed in 25 ml drug solution (10 minutes/day for 10 consecutive days). The changes of CSE induced cognitive dysfunction were evaluated by using different test methods such as colour recognition test; partition preference test; horizontal compartment test; and T-Maze tests. Further, the CSE exposure induced changes of biochemical parameters i.e., acetylcholinesterase activity; lipid peroxidation; reduced glutathione; and total protein levels were estimated in the brain of zebrafish. The pre-exposure of curcumin shown to produce the ameliorative effect against CSE induced neurocognitive impairments along with alteration of biochemical changes. Theseresults were comparable to reference control i.e., montelukast pre-treated group. Therefore, the curcumin can be served as newer medicines for immunological reaction associated neurocognitive disorders like Alzheimer and multiple sclerosis due to its potential anti-oxidative; anti-inflammatory; immunomodulatory; and acetylcholinesterase inhibitory actions.\n\nSUMMARYLoss of memory is a major problem in old age population. Curcumin used to treats the various neurological disorders. Curcumin possess the ameliorative potential in toxin induced neurocognitive function.

animal behavior and cognition↗