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Rahman, M. S.

Publications and source records attributed to Rahman, M. S..

At least 19 recordsLinked to original sources

Learning Strand-Equivariant Tokenizations of DNA with MirrorDNA

DNA has two strands, and for most regulatory label prediction tasks a sequence and its reverse complement should get same answer. Yet DNA language models are tokenized, trained and tested on one strand at a time. We show that this makes them inconsistent. BPE and $k$-mer tokenizers split 92--100\% of transcription-factor motifs differently on the two strands, and NT-v2, DNABERT-2 and HyenaDNA change 25-31\% of their predictions when the test sequences are reverse-complemented. We introduce {\model}, a compact DNA language model with a learned tokenizer that guarantees mirror-symmetric token boundaries across reverse-complement sequences, regardless of its learned parameters. We prove that this symmetry holds through the whole model. As a result, the same model can give identical answers on both strands when the label does not depend on the strand, and can still tell the strands apart when it does, which no strand-blind model can learn. Counting only predictions that are correct on both strands, \model\ more than doubles the MCC of NT-v2, DNABERT-2 and HyenaDNA. With 2.3M parameters, it is more accurate than the Caduceus models trained on the same data, and not significantly different from NT-v2 (98M parameters) on Genomic Benchmarks or from DNABERT-2 (117M) on the Nucleotide Transformer tasks. It also stays accurate on inputs sixteen times longer than those it was trained on. The same model trained with reverse-complement augmentation instead still changes about one prediction in ten with the strand, unless its outputs are averaged over both strands. Without any annotation, the tokenizer learns to keep the splice-donor signal \texttt{AGGT} in a single token. Code: https://github.com/NIRJHOR-DATTA/MirrorDNA.

bioinformatics↗

Antimicrobial resistance patterns reveal widespread multidrug-resistance among Vibrio species in shrimp hatchery environments of Bangladesh

Vibrio species are ubiquitous in shrimp hatchery systems, where their opportunistic pathogenic characteristics threaten the vulnerable larval stage, and antibiotics are routinely applied for disease control and prevention. Therefore, studying Vibrio composition and its antibiotic resistance burden is critical for hatchery environments and public health. The present study characterized Vibrio composition and its antimicrobial resistance patterns in water-flow systems and postlarvae from shrimp hatcheries in Coxs Bazar, Bangladesh. The findings revealed that Vibrio composition in these hatchery systems comprised nineteen different species. The Harveyi clade was the most dominant group, including V. alginolyticus, V. rotiferianus, and V. harveyi. The Vibrio isolates were highly resistant to erythromycin, ampicillin, and streptomycin, while remaining susceptible to chloramphenicol, nitrofurantoin, and gentamicin. Seven antibiotics, including trimethoprim-sulfamethoxazole, ampicillin, and erythromycin, were categorized as poorly active, suggesting their inefficacy against vibriosis outbreaks. More than 50% of the isolates had multiple antibiotic resistance index greater than 0.2 and 67.8% were categorized as multidrug-resistant. Both indices progressively increased along the water-flow systems and postlarvae had the highest values, pointing to antibiotic contamination within hatchery systems. Resistance gene screening identified sul2 and tetC as most prevalent, while association analysis showed cross-resistance patterns among antibiotics, concordance between trimethoprim-sulfamethoxazole and streptomycin resistance with the presence of sul2 and strA-strB genes, and co-selection of sul2, ermB, and strA-strB genes. The findings provide baseline data on Vibrio diversity and resistance burden, and inform antibiotic stewardship policies and monitoring strategies that support a One Health approach in shrimp hatchery systems.

microbiology↗

IMMF: An Interpretable Multi-Modal Framework for Hypothesis-Driven Biomarker Discovery in Triple-Negative Breast Cancer Using Public Data

Triple-Negative Breast Cancer (TNBC) is characterized by high heterogeneity, poor prognosis, and limited targeted treatment options. Bridging the gap between molecular alterations and histopathological morphology remains a major challenge in precision oncology. We propose an interpretable, multi-modal framework that integrates histopathological image analysis with multi-omics profiling (somatic mutations, DNA methylation, copy number alterations), leveraging U-Net-based nuclei segmentation, vision-language models (BLIP), biomedical language models (BioGPT), and explainable AI (SHAP, LIME). Our framework achieves strong predictive performance (AUC = 0.989) and provides transparent, biologically grounded interpretations by integrating morphological features with genomically prioritized biomarkers. Cross-modal analysis confirms established TNBC drivers and generates novel, testable hypotheses associating specific epigenetic alterations with distinct morphological phenotypes. While causal validation requires future wet-lab experiments, our framework accelerates hypothesis-driven biomarker discovery by integrating complementary data modalities with language-based reasoning, providing a transparent foundation for hypothesis generation and clinical translation.

bioinformatics↗

Interpretable biomarker discovery from small-sample microarray datasets using XGBoost rank aggregation and SVM-RFECV

MotivationHigh-dimensional microarray datasets remain valuable for cancer biomarker discovery, but their small sample sizes make robust and interpretable feature selection challenging. Efficient workflows are needed to derive compact gene signatures while preserving biological interpretability. ResultsWe developed a two-stage biomarker-discovery workflow that combines cross-validated XGBoost rank aggregation with support vector machine recursive feature elimination and cross-validation (SVM-RFECV) to identify compact candidate biomarker panels. The workflow was evaluated on 21 public binary and multiclass microarray datasets using repeated stratified cross-validation for internal validation. Across the dataset collection, the selected panels demonstrated strong internal discriminative performance while remaining sufficiently compact for downstream biological interpretation. SHAP analysis identified dataset- and class-specific discriminative genes, and functional enrichment analysis supported the biological coherence of representative consensus signatures. The proposed workflow provides an interpretable and reproducible framework for candidate biomarker discovery from small-sample microarray datasets. AvailabilitySource code and processed outputs are freely available at https://github.com/mashiyat-mahjabin-prapty/microarray-feature-selection.

bioinformatics↗

Sparse Autoencoders Reveal Structural and Family-level Features in BiRNA-BERT

RNA language models learn useful representations for structure and function, but the biological concepts encoded by their hidden states remain difficult to interpret. BiRNA-BERT is an RNA language model with adaptive byte-pair tokenization, making it an attractive target for mechanistic analysis. We present SPIRAL (Sparse autoencoders for Interpretable RNA Analysis), a layer-wise sparse-autoencoder (SAE) analysis of BiRNA-BERT that extracts interpretable sparse features while preserving the behaviour of the underlying language model. We train independent sparse autoencoders at layers 0, 5, and 11, each expanding the 768-dimensional hidden state into 6,144 dictionary features. Analysis of the learned features reveals biologically meaningful structure and family selectivity. Sparse features align with bpRNA nucleotide-level secondary-structure annotations and RNAcentral type labels: at layer 5, 44.3% of tested features show statistically significant structure association (mean enrichment of 1.61 x), and all 1,237 eligible features show significant RNA-type association. RNA-type-selective sparse profiles modestly improve k-nearest-neighbour balanced accuracy over dense BiRNA-BERT embeddings at layer 5. Together, these results show that sparse autoencoders can recover faithful, nucleotide-aware, and biologically interpretable feature decompositions from BiRNA-BERT.

bioinformatics↗

Proton motive force mediated efflux mismatch drives gentamycin-novobiocin collateral sensitivity in Pseudomonas aeruginosa

Resistance to a particular antibiotic can make bacteria sensitive to others, a phenomenon known as collateral sensitivity (CS). This study explored potential CS in clinical and experimentally evolved drug-resistant Pseudomonas aeruginosa (PA) and investigated underlying mechanisms. Whole-genome sequencing and RNA-seq were analyzed to identify genetic and transcriptional correlations. In vitro efficacies were assessed with co-and sequential-exposure regimens. Multiple CF isolates and experimentally evolved gentamycin (GEN) resistant strains consistently exhibited strong CS to novobiocin (NOV). Comparative genomics revealed pmrB gain-of-function mutations, which was further supported by transcriptomic signatures of pmrAB activation. Transcriptomic data suggests potential outer-membrane remodeling characterized by polyamine accumulation and compromised porin channel expression. Additionally, the reduction in proton motive force (PMF) further explains the possible mechanism underlying GEN resistance. As NOV efflux is PMF-dependent, this energetic deficit created a PMF-efflux mismatch, leading to hypersensitivity to NOV. Notably, sequential GEN[->]NOV treatment effectively restricted the emergence of GEN resistant subpopulations. Overall, our data suggest GEN resistance in PA may arises through envelope remodeling and reduced PMF, which impairs efflux pumps and creates hypersensitivity to NOV. Exploiting this PMF-efflux mismatch with sequential treatment effectively restricted the emergence of GEN resistance.

microbiology↗

In vitro investigation and evaluation of the antidiabetic potential of the ethanolic extract of Asparagus racemosus using starch digestion, glucose diffusion, glucose uptake, and DPPH assays

Asparagus racemosus commonly known as Shatamull, is a medicinal plant with pharmacological applications documented in both Indian and British Pharmacopoeias and various traditional medicinal practices. Previous studies have reported that A. racemosus reduces hyperglycemia by enhancing insulin secretion. The aim of the current study was to assess the antihyperglycemic actions and explore the underlying mechanisms of action of A. racemosus utilizing in vitro carbohydrate digestion, glucose diffusion, glucose uptake, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and preliminary phytochemical screening. The inhibition of carbohydrate digestion was assessed using -amylase and -glucosidase enzyme assays. The effect on glucose diffusion was evaluated using cellulose ester dialysis tube. Subsequently, glucose uptake was measured in a yeast cell model at different glucose concentrations, and the antioxidant potential was evaluated by measuring DPPH radical scavenging activity. A. racemosus significantly reduced (p<0.05- 0.01) glucose release during in vitro starch digestion by 21.11%, whereas glucose absorption decreased by 22.75% (p<0.05-0.001). The most significant enhancement (p<0.05-0.001) in glucose uptake by 65.03%, was observed at 5 mM glucose concentration. Furthermore, it showed significant antioxidant activity by scavenging DPPH (p<0.05, 0.001) radicals by 42.46%. Preliminary phytoconstituent screening indicated the existence of flavonoids, tannins, steroids, glycosides and saponins. In conclusion, A. racemosus shows an inhibitory effect on carbohydrate digestion and absorption, enhances glucose uptake and demonstrates significant DPPH radical scavenging activity, potentially due to the presence of naturally occurring phytochemicals. Thus, A. racemosus may contribute as a promising antidiabetic drug for the treatment of diabetes mellitus. More investigations are needed to determine the active compounds in A. racemosus that contribute to its antidiabetic effects.

pharmacology and toxicology↗

Dietary Lees Supplementation Enhances Poultry Health Performance Through Gut Ecosystem Reprogramming

The search for sustainable alternatives to in-feed antibiotics has intensified with the global antimicrobial resistance crisis. While microbial by-products show potential, their mechanisms remain elusive. This study reveals that spent yeast lees, a fermentation by-product, profoundly reprograms the chicken gut ecosystem to enhance growth. We investigated the differential effects of live spent lees versus autoclaved spent lees from a molasses fermenter with Saccharomyces cerevisiae. In a 14-day controlled trial, 0-day-old poultry chicks (n=15) were assigned to a control diet (n=5), a live spent Lees-supplemented diet (n=5), or an autoclaved spent Lees-supplemented diet (n=5). Through the feeding trial with either live spent Lees or autoclaved spent Lees, we demonstrate significant enhancement of growth performance, with autoclaved spent Lees achieving the highest final body weight (573.4 {+/-} 17.2 g). Using deep shotgun metagenomic sequencing of faecal samples, we demonstrate that both spent Lees forms induced a dramatic ecological shift, driving the gut microbiome to a state of monodominance by Bacteroides fragilis (reaching 74.83% with live spent Lees). This was accompanied by the near-complete eradication of enteropathogens like like Enterococcus faecium and Escherichia coli. Crucially, live spent Lees supplementation effectively countered a natural age-dependent expansion of the gut resistome, eliminating the high-risk oxazolidinone resistance gene o23S and restructuring the virulome away from offensive effector systems. However, this beneficial restructuring came at the cost of significantly reduced microbial diversity and suppression of beneficial commensals. A key finding was that autoclaved spent Lees, while inducing a less extreme microbial shift, yielded superior final body weight, suggesting its lysed cells provide enhanced nutritional availability. Our work establishes spent yeast Lees not as mere waste, but as a potent, multi-functional supplement that enhances growth through gut ecosystem engineering, yet necessitates a strategic choice between its live and autoclaved forms based on production priorities.

microbiology↗

Modeling Temporal Dependencies and Feature Interactions Reveal Novel Clinical and Molecular Insights into Alzheimer's Disease Progression

ObjectiveAlzheimers Disease remains a major public health challenge, requiring insights into feature interactions and temporal trends of feature importance. Community-wide data science competitions such as the TADPOLE Challenge provide platforms to benchmark predictive models using ADNI datasets. While top-performing models achieve accurate predictions, they often leave mechanistic questions unresolved. We introduce a framework that separately models static feature interactions and temporal dynamics, enabling complementary insights from longitudinal AD data. Materials and MethodsWe analyzed XGBoost with TreeSHAP for feature interactions and RNN-AD with Integrated Gradients for temporal trends. This two-branch design allows XGBoost to capture nonlinear cross-sectional interactions, while RNN captures evolving, time-dependent influences. The attributions are fused into a combined importance map. ResultsOur framework showed agreement between TreeSHAP and IG, highlighting FAQ, CDRSB, ADAS13, MMSE, and RAVLT variants as the most consistently important features across both branches. Temporal attribution analysis revealed stage-dependent trends: in CN, features such as DX:CN, FAQ, and RAVLT_immediate increased in importance with longer prediction horizons; in MCI, MidTemp and WholeBrain gained importance; and in AD, FAQ remained dominant. Feature-interaction analysis identified strong clinical-clinical interactions and secondary clinical-molecular interactions involving hippocampal and entorhinal volumes. DiscussionCombining interaction and temporal trends showed that RAVLT_immediate, FAQ, and DX-based features were the only markers consistently influential across both dimensions, indicating stable, cross-validated predictors of Alzheimers disease progression. Feature importance in AD prediction is dynamic, with early-time features often most influential. These insights support personalized monitoring, adaptive modeling, and mechanistic interpretability, enhancing patient-specific interventions and trial design. ConclusionThis work highlights feature interactions and temporal trends in AD prediction models, offering insights for personalized treatments and patient-specific trial designs. Our framework provides stable, cross-validated explanations that unify structural and temporal importance, enhancing trustworthiness and mechanistic interpretability in AD modeling.

neuroscience↗

Supervised Factorization to Associate Spatial Transcriptomics with Complementary Molecular Readouts

Spatial Transcriptomics enables studying gene expression data within spatial context of tissues. Yet understanding how spatial molecular phenomena influence transcriptional patterns remains a key challenge. We propose a novel supervised Non-negative Matrix Factorization (NMF) framework, where supervision is selectively and explicitly applied to guide the learning of a supervised spatial factor. This distinguishes our method from prior approaches by enforcing spatial alignment only on a targeted component of the factorization, enabling biologically interpretable associations between gene expression and spatial molecular events. This approach also enables the identification of genes whose expression patterns are spatially correlated with molecular events of interest. Applied to datasets involving Alzheimers Disease (AD) and Myocardial Infarction (MI), our method successfully discovered supervised spatial factor associated with disease related signal. In the case of Alzheimers Disease (AD), we have presented a spatial decay model to represent how the influence of amyloid-beta plaque signals diminishes with distance, and used this as a supervision signal during matrix factorization. Applied across both disease contexts, our method successfully identified biologically meaningful gene sets associated with disease progression. By ranking genes based on their contribution to the supervised spatial factor, the framework highlights candidate genes potentially involved in disease-related processes.

bioinformatics↗

Antidiabetic effects of astaxanthin partly mediated by the inhibition of carbohydrate digestion and absorption, and in vitro DPPH and lowering lipids in high-fat-fed albino mice

Astaxanthin (ASX) has been reported to reduce hyperglycemia by improving insulin secretion and insulin resistance. The present research aims to elucidate the antidiabetic effects as well as the mode of action of ASX, both in-vitro and in-vivo. Starch digestion, glucose diffusion, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were investigated in vitro, and oral glucose tolerance tests (OGTT), total residual unabsorbed sucrose contents in the gut, gastrointestinal (GI) motility were assessed in high-fat-fed (HFF) hyperlipidemic albino mice. Acute and chronic metabolic effects were evaluated by monitoring food and water intake, amount of urination and defecation. HFF-induced type 2 diabetic mice were treated for 33 days with ASX (30 and 60 mg/5 ml/kg b.w.) were used to assess chronic effects. In the in vitro study, ASX (1.6 - 1000 {micro}g/mL and 40 - 5,000 {micro}g/ml) decreased (p<0.001) enzymatic digestion of starch and glucose diffusion by 45.14% and 32.50%, respectively and also showed a significant inhibitory effect on the DPPH (p<0.001) over a concentration range (1.6 - 5000 {micro}g/mL) of ASX. During the in vivo experiments, oral administration of ASX (30 - 60 mg/5 ml/kg b.w.) improved oral glucose tolerance (p<0.001) as well as significantly increased (p<0.01) residual unabsorbed sucrose contents in the six segments of the gut. In addition, ASX (30 - 60 mg/5 ml/kg b.w.) significantly enhanced GI motility (p<0.05) in albino mice. Furthermore, ASX (60 mg/5 ml/kg b.w.) reduced food and fluid intake, and the amount of urine and stool formation significantly (p<0.001) both in chronic and acute metabolic studies, accordingly. In a chronic study, ASX, at (30 and 60 mg/5 ml/kg b.w.), substantially lowered blood glucose, total cholesterol, VLDL, triglycerides, LDL cholesterol and also improved liver glycogen content. In conclusion, ASX shows effect on decreasing carbohydrate digestion, absorption, increasing GI motility, and inhibiting DPPH. Thus, ASX might be a potential drug for the management of diabetes and its complications.

pharmacology and toxicology↗

Elucidating the perception, awareness and biosecurity practices among the live poultry/poultry-meat sellers to mitigate the risk of zoonotic salmonellosis

Zoonotic salmonellosis remains a major public health concern, especially in low-resource settings where poultry handling practices are often informal. Biosecurity measure of live poultry/poultry-meat vending shop is necessary to address this zoonoses. This study investigated the knowledge, attitudes, and biosecurity practices of poultry/poultry-meat sellers toward the risk of zoonotic salmonellosis in Bangladesh. A quantitative, descriptive, cross-sectional study was conducted among the 432 poultry/poultry-meat sellers through a structured questionnaire in multistage sampling approach. Majority of the poultry/poultry-meat sellers (n=432) were male (75.5%), age between 26-34 years (31.9%), had primary education (28.9%), experience of [&le;]5 years (40.3%), and monthly income was <20000 BDT (43.3%). Additionally, minimal had training on live poultry marketing (33.1%), and poultry-meat processing and marketing (28.5%). The 33.34% and 62.03% of poultry/poultry-meat sellers had the good knowledge and positive attitudes respectively. While 41.43% were involved in correct biosecurity practice. Moreover, the mean KAP score was 53.12{+/-}0.89, 68.59{+/-}0.79 and 54.58{+/-}0.73 respectively. From the multivariate analyses, higher education was a strong predictor of good knowledge (Bachelors degree: OR=6.64, 95%CI:2.59-17.04, p<0.01), positive attitude (Bachelors degree: OR=13.48, 95%CI:3.72-48.87, p<0.01), and correct biosecurity practices (HS: OR=5.52, 95%CI:2.62-11.63, p<0.01; Bachelors degree: OR=4.81, 95%CI:2.03-11.39, p<0.01). The sellers with good knowledge, positive attitudes, and correct biosecurity practices perceived higher zoonotic risk (median=7, p<0.05), with perception co-relation that significantly influenced by education (r=0.131, p<0.01) and training (r=0.084, p<0.05). Despite moderate awareness, sellers showed notable gaps in safe practices, highlighting the need for practical training that enhances risk perception, promotes behaviour change, and builds hands-on biosecurity skills.

scientific communication and education↗

A Transient Increase in Cardiomyocyte Protein O-GlcNAcylation Enhances Susceptibility to Pressure Overload-Induced Cardiac Remodeling

BACKGROUNDThe observation that diabetic patients always under tight-glycemic control consistently show better cardiovascular disease outcomes compared to patients who transition to tight-glycemic control after prior conventional glycemic control lead to the concept of metabolic memory. Mechanisms such as epigenetics possibly mediate the lasting metabolic memory effects, our understanding of the underlying mechanisms remains limited. Increased cardiac protein posttranslational O-linked {beta}-N-acetylglucosamine (O-GlcNAc) modification is implicated in cardiac remodeling observed in diabetes, and our previous work shows chronically elevated cardiomyocyte O-GlcNAc causes adverse cardiac changes. Therefore, the current study hypothesized that transiently increased cardiomyocyte O-GlcNAcylation leads to exacerbated adverse cardiac remodeling after subsequent pressure-overload. METHODS AND RESULTSUsing our previously described inducible cardiomyocyte specific, dominant-negative O-GlcNAcase (dnOGAh) mouse and single transgenic littermate controls (Con), we induced O-GlcNAc levels for 2wk (ON), followed by a 2wk washout (OFF); mice then underwent transverse-aortic constriction (TAC) or Sham surgery. We observed the expected cardiac remodeling in TAC groups, including decreased cardiac function, and increased hypertrophy and fibrosis. Moreover, these pathologic measures were exacerbated in the ON/OFF-TAC vs. Con-TAC mice; additionally, transcriptomic analysis of LV-tissue from each experimental group showed pathways which not only supported our fibrosis, hypertrophy and functional results of exacerbated cardiac remodeling, but also, revealed potential novel molecular pathways underlying this pathologic remodeling. CONCLUSIONSWe observed exacerbated cardiac pathology between ON/OFF-TAC vs. Con-TAC groups supporting the concept of "O-GlcNAc memory" as a component of metabolic memory. Moreover, transcriptomic analysis provides insight into potential molecular pathways underpinning this metabolic/O-GlcNAc memory such as Ccn2/CTGF-driven fibrosis, and/or Nox4-driven oxidative stress. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/657956v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@717ea9org.highwire.dtl.DTLVardef@132bdcaorg.highwire.dtl.DTLVardef@4a2bdaorg.highwire.dtl.DTLVardef@18508d9_HPS_FORMAT_FIGEXP M_FIG C_FIG Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIWe provide a novel paradigm to study phenotypic and molecular effects of specific, transiently increased cardiomyocyte O-GlcNAcylation on the heart. C_LIO_LIOur results show exacerbated adverse cardiac remodeling due to transiently increased cardiomyocyte O-GlcNAc with pressure-overload, supporting the concept of "O-GlcNAc memory" as a component of metabolic memory. C_LIO_LITranscriptomic insights show gene expression basis for not only observed exacerbated adverse cardiac remodeling (e.g., hypertrophy, fibrosis, cardiac dysfunction), but also potential molecular pathways that could drive cardiac pathology exacerbation of O-GlcNAc memory. C_LI What are the clinical implications?O_LIThis study supports a concept of "O-GlcNAc memory", where previously increased cardiomyocyte protein O-GlcNAcylation can impact the later development of differential cardiac pathology--like the pathology seen in metabolic memory research. C_LIO_LIThe potential role of O-GlcNAc in mediating metabolic memory will help focus future translational research on this modification and downstream cardiac effects in diabetes. C_LIO_LITranscriptomic profiling of cardiac remodeling in this model provides an investigational roadmap for future molecular and functional studies to identify novel therapeutics that ameliorate heart disease induced by differential metabolic memory. C_LI

molecular biology↗

ORANGE: A Machine Learning Approach for Modeling Tissue-Specific Aging from Transcriptomic Data

Despite aging being a fundamental biological process which profoundly influences health and disease, the interplay between tissue-specific aging and mortality remains underexplored. This study applies machine learning on GTEx transcriptomic data to model tissue-specific biological ages across 12 different types of tissues and introduces an age-gap metric to quantify deviations from the chronological age. We use several modeling techniques optimized with three feature selection strategies: Pearson correlation, age-related differentially expressed genes, and tissue-enriched genes (expressed at least fourfold higher in a specific tissue). Among these, Pearson correlation combined with elastic net regression yields the best performance, with models achieving an average RMSE of 6.44 years and an R2 of 0.64. To quantify deviations from chronological age relative to the population, we train neural networks to regress predicted ages against chronological ages, and subtract their outputs from the predicted ages to calculate a metric which we call the age-gap. Age-gap statistics reveal significant tissue-specific aging patterns, identifying extreme agers and correlations between extreme aging and mortality. About 20% of subjects are found to exhibit extreme aging in one tissue, while 1% show multi-organ aging. Further analysis reveals that accelerated aging in specific tissues correlates with with greater risk of death from illness. These findings greatly emphasize the role of transcriptomics in aging research and its implications for health and longevity.

bioinformatics↗

CRISMER: A transformer-based Interpretable Deep Learning Approach for Genome-wide CRISPR Cas-9 Off-Target Prediction and Optimization

CRISPR-Cas9 gene editing holds transformative promise for genetic therapies, but is hindered by off-target effects that undermine its precision and safety. To address this, we developed CRISMER, a hybrid deep-learning architecture that uses multi-branch convolutional neural networks to extract k-mer features and transformer blocks to capture long-range dependencies. This hybrid approach enhances the prediction and optimization of single-guide RNA (sgRNA) designs. CRISMER was trained on Change-seq and Site-seq datasets, using a 20 x 16 sparse one-hot encoding scheme, and evaluated on independent datasets including Circle-seq, Guide-seq, Surro-seq, and TTISS. CRISMER outperformed existing tools, achieving an F1 score of 0.728 and a PR-AUC of 0.818 on the CRISPR-DIPOFF dataset, and it generalized to fully independent datasets and to off-targets containing insertions and deletions. Ablation experiments confirmed that each architectural component contributes to performance, and CRISMER attained these results with substantially fewer parameters than transformer-and foundation-model baselines. It also demonstrated strong in silico specificity prediction and optimization capabilities, identifying sgRNA variants for targets such as PCSK9, BCL11A, and EXM1 with improved predicted off-target profiles. Interpretability analysis via integrated gradients confirmed the models focus on critical PAM-proximal regions and mismatch patterns. These results demonstrate that CRISMER significantly improves the accuracy and safety of CRISPR-Cas9, advancing its reliability for therapeutic applications.

bioinformatics↗

Investigating the prognostic value of KCNN4 gene expression in human pancreatic adenocarcinoma by bioinformatic analysis

Finding accurate biomarkers for early detection and prognosis is critical because pancreatic adenocarcinoma (PAAD) is a deadly cancer with a poor prognosis. Though its function in PAAD is still unknown, the gene KCNN4, which codes for a calcium-activated potassium channel, has been linked to a number of malignancies. In this work, the cancer studies of the CPTAC, TCGA, and GTEx projects were targeted using a thorough database mining technique. Several analytical methods were used to examine full-scale molecular, expression, and prognostic profiles of the KCNN4 gene in pancreatic adenocarcinoma tissues. It was discovered that the majority of the cancerous tissue had different levels of mRNA and protein expression for this gene. The results of comparative immunohistochemistry also revealed that normal pancreatic tissues had reduced expression of the KCNN4 protein. An analysis overview of copy-number alterations and KCNN4 mutations in PAAD samples was also conducted. Furthermore, there was a correlation found between the expression of KCNN4 and both overall and disease-free survival in pancreatic adenocarcinoma. In pancreatic adenocarcinoma tissue, co-expressed genes of KCNN4 were found to be involved in cell maintenance-related functions, according to gene coexpression, additional ontology, and pathway analysis. When it comes to cancer diagnosis and treatment, the experimental findings of this study should aid in integrating KCNN4 into clinical applications.

bioinformatics↗

Computational Evaluation of Phytochemicals as Potential Anti-HIV Drugs Targeting CCR5 and CXCR4 Receptors

HIV is a major worldwide health concern; hence new therapeutic approaches are needed to fight viral resistance and enhance treatment results. HIV entrance into host cells depends on the CCR5 and CXCR4 receptors, which makes them potential targets for antiviral medication development. The objective of this study is to computationally evaluate 53 phytochemicals that target CCR5 and CXCR4 as potential anti-HIV medications. Effective anti-HIV medications were projected to be phytochemicals that may inhibit these receptors and so interfere with the HIV life cycle. AutoDock Vina was used to perform the molecular docking investigation from which six phytochemicals capable of inhibiting CCR5 and CXCR4 were identified based on the lowest docking score. i.e., Withaferin A, Oleanolic Acid, Ursolic Acid, Theaflavine, Camptothecin, and Hypericin. The SWISSADME server was utilized to decide their druglikeness properties, the ADMETlab server to predict different pharmacokinetic and pharmacodynamic properties, the PASS-Way2Drug server to evaluate their activity spectra, and the RS-WebPredictor server to figure out the metabolism in the body. They adhered to Lipinskis rule of five and had promising ADME/toxicity study result along with favorable molecular dynamics simulation. Overall, the above-mentioned six phytochemicals might have the potential to be used as alternative HIV therapeutics.

bioinformatics↗

StackGlyEmbed: Prediction of N-linked Glycosylation sites using protein language models

N-linked glycosylation is one of the most basic post-translational modifications (PTMs) where oligosaccharides covalently bond with Asparagine (N). These are found in the conserved regions like N-X-S or N-X-T where X can be any residue except Proline (P). Prediction of N-linked glycosylation sites has great importance as these PTMs play a vital role in many biological processes and functionalities. Experimental methods, such as mass spectrometry, for detecting N-linked glycosylation sites are very expensive. Therefore, prediction of N-linked glycosylation sites has become an important research field. In this work, we propose StackGlyEmbed, a stacking ensemble machine learning model, to computationally predict N-linked glycosylation sites. We have explored embeddings from several protein language models and built the stacking ensemble using SVM, XGB and KNN learners in the base layer, with a second SVM model in the meta layer. StackGlyEmbed achieves 98.2% sensitivity, 92.5% balanced accuracy, 89.1% F1-score and 82.6% MCC in independent testing, outperforming the existing SOTA methods. StackGlyEmbed is freely available at https://github.com/nafcoder/StackGlyEmbed.

bioinformatics↗