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Datta, A.

Publications and source records attributed to Datta, A..

At least 37 records · Page 2Linked to original sources

Fast Fourier Transform is a training-free, ultrafast, highly efficient, and fully interpretable approach for epigenomic data compression

Improving the efficiency of data compression remains essential for feature selection and data modelling. Current approaches for compressing epigenomic/genomic data highly rely on autoencoder that requires substantial computing resources, parameter fine-tuning, training, and time. Here, we developed a training-free, Fast Fourier Transform (FFT)-based method, for data compression with high efficiency and full interpretability. Our FFT method compresses epigenomic data of histone modification up to 1,000-fold while still maintaining high reconstruction fidelity (cosine similarity, 99.7%), does not require any training and completes ultrafast within 70 milliseconds on GPU or 20 seconds on CPU opposite to extensive training in hours/days for autoencoder on GPU/CPU, and offers full interpretability of compressed features from frequency components of original signals in contrast to the uninterpretable "black box" from autoencoder. This enables high accuracy in the classification model prediction (AUC, 0.960). Thus, our novel FFT method represents a major paradigm shift in data compression.

bioinformatics↗

A novel deep learning method using contrastive learning enables interpretable outputs from relationships between gene expression and histone modification

Current methods for predicting gene expression from histone modifications rely on arbitrary binary classification thresholds such as the median to distinguish between high and low expression for genes. This approach lacks biological justification, creates dataset-dependent classifications, and ignores the relative regulatory relationships between genes that are often more biologically meaningful than absolute cutoffs. We introduce a novel pairwise ranking approach that compares relative expression levels between gene pairs based on their histone modification patterns, eliminating arbitrary threshold selection. Evaluation using the REMC E066 and GSE76344 datasets showed that our pairwise classification framework demonstrated consistent ranking performance in both datasets. The ablation study found that only a subset of histone modification types is necessary, giving evidence of redundancy in the biological code.

bioinformatics↗

What's next for Indian Ornithology? 101 key research questions

India has a rich history of ornithology, and bird research in this field has expanded considerably in recent decades, spurred by a growing number of birdwatchers and ornithologists. Despite this progress, critical gaps remain. This paper highlights key areas where further research is needed and identifies pressing questions that will shape Indian ornithology in the coming years. Drawing from diverse inputs, we present a curated list of 101 research questions spanning across the various disciplines in ornithology - Natural History, Physiology and Disease Ecology, Behaviour, Population and Community Ecology, Habitat Ecology, Macroecology and Biogeography, Population Genetics and Evolution, Applied/Economic Ornithology and Conservation. The list was compiled through a multi-stage process, starting with a public open call for questions, followed by review and curation by a smaller panel of subject specialists. Each question was independently scored by a panel of experts based on three criteria: generality, novelty, and relevance. To account for variation in scoring styles, scores were normalised using Z-scores. The top 101 research questions were then selected based on these standardised scores. Each question is accompanied by an annotation that describes the significance of the question, and highlights opportunities to address it. While our list of research questions highlights significant research priorities, it is not intended to be exhaustive. Rather, it reflects the perspectives of those involved in its curation, who deemed these questions particularly relevant and impactful towards advancing Indian ornithology. We expect these questions to spark new project ideas among students, researchers, and citizen scientists, while guiding funders, managers, and policymakers toward priority research areas.

ecology↗

Anti-isoDGR Antibody Inhibits Atherosclerosis Induced by Western Diet in ApoE-/- mice

BackgroundDegenerative protein modifications (DPMs) accumulate with aging and can alter biomolecule structure and function, including via spontaneous conversion of Asn-Gly-Arg (NGR) to isoAsp-Gly-Arg (isoDGR) motifs that can bind integrins and drive chronic inflammation. Since isoDGR-modified extracellular matrix proteins are enriched in atherosclerosis and have been associated with rupture-prone plaque characteristics, we hypothesized that antibody neutralisation can inhibit key pathological features including atherosclerotic vascular plaque formation and metabolic dysfunction. MethodsWe first examined Pcmt1-/- mice which rapidly accumulate isoDGR due to lack of the corresponding repair enzyme to assess the extent of vascular protein damage. We then treated 6-8 week old atherosclerosis-prone (ApoE-/-) mice which were fed a high-fat Western diet (WD) with weekly dose of 1mg/kg isoDGR-specific monoclonal antibody (isoDGR-mAb) or isotype-matched control (while on diet) for 2 months duration. A regular chow-fed ApoE-/- group served as baseline control. Aortic atherosclerotic burden, plaque composition, systemic inflammation, lipid profiles, hepatic steatosis, and metabolic parameters (indirect calorimetry) were assessed. ResultsPcmt1-/- mice displayed extensive isoDGR deposition and degeneration of the aortic wall, linking this DPM to vascular structural damage. In the ApoE-/- mice, WD induced large aortic root plaques with abundant isoDGR and macrophage infiltration. IsoDGR-mAb treatment decreased plaque size by [~]30% with reduced lipid and collagen content (p=0.001). Furthermore, plaques in treated mice contained significantly fewer CD68+ macrophages that also exhibited limited activation. Systemically, isoDGR-mAb modified lipoprotein profiles by decreasing atherogenic VLDL/IDL/LDL cholesterol (p=0.04) while slightly increasing HDL, accompanied by a reduction in circulating inflammatory proteins. IsoDGR-mAb also protected against hepatic lipid accumulation which was reduced by [~]60% in treated animals (p<0.001), with indirect calorimetry confirming [~]30% higher oxygen consumption and energy expenditure without change in food intake or physical activity. ConclusionWe identified isoDGR as a key pathological factor involved in the progression of atherosclerosis. Remarkably, isoDGR neutralization diminished plaque inflammation and improved atherosclerotic plaque stability. Our findings support isoDGR neutralization as a promising therapeutic strategy to mitigate both atherosclerosis and aging-associated metabolic dysfunction.

pharmacology and toxicology↗

Multi-year study on the effects of elevated CO2 in mature oaks unravels subtle metabolic adjustments but stable biotic stress resistance

O_LIRising atmospheric CO2 levels are predicted to influence forest health directly and indirectly, yet the long-term effects of elevated CO2 (eCO2) on mature trees in natural ecosystems remain poorly understood. Understanding how eCO2 affects susceptibility to biotic stress and alters leaf metabolism is critical for predicting forest responses to climate change. C_LIO_LIWe examined the effects of eCO2 (+150 ppm) on 180-year-old Quercus robur at the Birmingham Institute of Forest Research (BIFoR) Free Air CO2 Enrichment (FACE) facility. From 2016 (pre-treatment) to 2024 (year 8 of enrichment), we monitored natural powdery mildew infection and insect herbivory, alongside targeted and untargeted metabolomic profiling of leaf material collected across the growing season. C_LIO_LIWhile seasonal patterns and an overall decline in PM and herbivory were observed, no consistent differences in biotic stress incidence emerged due to eCO2. Metabolomic data revealed subtle but widespread shifts, especially in amino acid, CoenzymeA, and redox pathways. C_LIO_LIThese results suggest that although eCO2 drives extensive metabolic changes, it does not alter biotic stress resistance in mature oaks. Instead, eCO2 appears to promote physiological plasticity that may shape future responses to combined environmental stressors. These insights offer a valuable reference point for interpreting long-term ecosystem dynamics. C_LI

plant biology↗

MRI-free Virtual Neuronavigation for TMS

Methods to determine coil position are paramount in TMS. Existing approaches are limited to scalp heuristics or depend on some combination of neuronavigation hardware, average brain templates, as well as subject MRI and/or evoked responses. We developed head-model guided TMS virtual neuronavigation without subject MRI, specialized hardware, or evoked responses. The MRI-free virtual neuronavigation involves three scalp measurements which are then used to generate an individualized head model by applying ellipsoid-based affine transformations to the MNI standard head model. Virtual neuronavigation is then performed on this individualized head model for any brain target. The coil position is then provided to the operator in simple geodesic measurements. We simulated this process on MRI data of fifteen subjects showing a mean error of 2.75 mm, outperforming the accuracy of scalp heuristic targeting approaches.

bioengineering↗

TRPV1 Defends the Healthy Murine Cornea against Staphylococcus aureus Adhesion Independently of Sensory Nerve Firing

PurposePreviously we showed that transient receptor potential ion channels TRPA1 and TRPV1 selectively protect the cornea against bacterial adhesion, with TRPA1 countering the Gram-negative pathogen Pseudomonas aeruginosa and TRPV1 countering environmental bacteria. Here, we explored parameters of this specificity using a Gram-positive pathogen Staphylococcus aureus. MethodsHealthy corneas of C57BL/6J wild-type (WT), TRPA1 (-/-) or TRPV1 (-/-) mice were challenged with S. aureus for 4 or 6 hours. Some experiments instead/also used resiniferatoxin (RTX) to deplete TRPV1-expressing nerves, JNJ-17203212 to selectively antagonize TRPV1, or the anesthetic bupivacaine to inhibit nerve firing. Adherent bacteria were quantified using FISH labeling (16S rRNA-targeted probe). Lyz2+, CD11c+ and CD45+ cells were visualized/quantified using hybrid mT/mG + LysMcre mice (red cell membranes; Lyz2+-GFP), CD11c+-YFP mice, and anti-CD45-antibody respectively. ResultsCorneas of TRPV1 (-/-) not TRPA1 (-/-) mice were found more susceptible to S. aureus adhesion compared to WT. Accordingly, either ablation of TRPV1-expressing nerves or TRPV1 antagonism increased adhesion. Defense against S. aureus adhesion did not depend on nerve firing. Despite having no significant impact on CD11c+ or Lyz2+ cell numbers, S. aureus challenge increased CD45+ cell counts, also dependent on TRPV1-expressing nerves, and it increased Lyz2+ cell sphericity and volume. ConclusionHealthy corneas utilize TRPV1 to protect against S. aureus adhesion independently of sensory nerve firing. This contrasts with defense against P. aeruginosa adhesion which requires TRPA1 and nerve firing. How the differential immune cell responses to these two pathogens relate to TRP-dependent defense against adhesion remains to be determined.

microbiology↗

Differential interfacial tension between oncogenic and wild-type populations forms the mechanical basis of tissue-specific oncogenesis in epithelia

Why does the same oncogenic mutation drive tumor formation in some tissues but not in others? While cancer driver mutations are well-documented, their tissue-specific effects remain largely attributed to genetic factors, leaving the biophysical aspects underexplored. Here, we demonstrate that mechanical interactions, specifically interfacial tension between newly transformed and wildtype epithelial cells are critical in determining survival and growth of HRasV12 oncogenic mutants in human mammary and bronchial epithelia, leading to contrasting outcomes in the two tissues. In mammary epithelium, isolated oncogenic cells are extruded-a typical mechanism of defense against cancer in epithelia-while oncogenic groups become spatially confined in a kinetically arrested, jammed state, marked by an actomyosin belt at the interface. In contrast, bronchial epithelium permits persistent spreading of the same oncogenic cells, which form long protrusions regardless of colony size. Furthermore, oncogenic clusters in these two tissues exhibit distinct biophysical properties, including variations in cell shapes, intracellular pressure, cell-cell tension, and cellular motility. Using a cell shape-tension coupled bi-disperse vertex model, we reveal that differences in interfacial tension at mutant-wild-type boundaries dictate whether oncogenic cells are eliminated, restrained, or expanded and that modulating the heterotypic interfacial tension alters mutant cell fate within the epithelium. Together, our findings uncover a mechanical basis for tissue-specific oncogenesis by highlighting how differential cellular mechanics at the oncogenic-host cell interface regulate tumor initiation and progression.

biophysics↗

Targeting Colorectal Cancer Liver Metastasis Through Repurposing Metabolic and Immune Inhibitors : A Theoretical Study

Liver metastasis from colorectal cancer is a major cause of death in patients with advanced colorectal cancer (CRC) and remains a difficult challenge in oncology. Inspite of commnedable developments in medical inventions, the complexity and poor prognosis of metastatic stage, alliterative strategies are required to address Colorectal cancer liver metastasis (CRLM). This paper presents a computational study on drug repurposing for CRLM using a Boolean Network model. We comprehensively analyze CRLM signaling pathways such as WNT, PI3K/AKT/mTOR, MAPK, Hedgehog, TGF-{beta}, NF-kB, NOTCH and HGF and target them with metabolic and immune inhibitors. This study utilizes a computational analysis to evaluate single and multi-agent treatments across scenarios involving single and multiple genetic mutations. Our findings highlights the efficacy of metabolic inhibitors such as Simvastatin, Metformin, and predict compatible partner drugs to enhance their effiacy. Additionaly, we predict possible improvements for CRLM treatment using an immunotherapy drug like Pembrolizumab. Overall, this paper provides new insights into drug repurposing to improve CRLM treatment outcomes.

cancer biology↗

On the need of individually optimizing temporal interference stimulation of human brains due to inter-individual variability

IntroductionTranscranial temporal interference stimulation (TI, TIS, or tTIS), also known as interferential stimulation (IFS), is able to focally stimulate deep brain regions, provided it is properly optimized. We previously presented an algorithm for optimizing TI using two arrays of electrodes and showed that it can achieve more focal stimulation compared to optimized high-definition transcranial electrical stimulation (HD-TES) and conventional optimized TI using two pairs of electrodes, especially in the deep brain areas such as the hippocampus. However, those modeling studies were only performed on an averaged head (MNI152 template) and three individual heads without exploring inter-individual variability. Existing TI works in the literature mostly utilize a common (possibly optimized) montage of two pairs of electrodes on different individual heads without considering inter-individual variability. Material and methodHere we aim to study the inter-individual variability of optimized TI by applying the same optimization algorithms on N = 25 heads using their individualized head models. Specifically, we compared the focality achieved by different stimulation techniques at six different regions of interest (ROI; right hippocampus, left dorsolateral prefrontal cortex, left motor cortex, right amygdala, right caudate, and left thalamus) under both individually optimized and unoptimized montages. We also conducted numerical sensitivity analysis on the individual optimization and performed phantom recordings to test our models. ResultsAs expected, there is a variability in focality achieved by TI of up to 1.2 cm at the same ROI across subjects due to inter-individual differences in the head anatomy and tissue conductivity. We show that optimized TI using two arrays of electrodes achieves higher focality than that from optimized HD-TES at the same level of modulation intensity at 5 of the 6 ROIs. Compared to using a common montage either optimized from the MNI152 template or from the literature, individually optimized TI using two pairs of electrodes improves the focality by up to 4.4 cm, and by up to 1.1 cm if using two arrays of electrodes. Focality achieved by the individual optimization is sensitive to random changes and can vary up to 9.3 cm due to the non-lienarity of TI physics. Experimental recordings on a head phantom confirms the drop in TI stimulation strength when using unoptimized montages as predicted by our in silico models. ConclusionThis work demonstrates the need of individually optimizing TI to target deep brain areas, and advocates against using a common head model and montage for TI modeling and experimental studies.

biophysics↗

A Vascularized Liver Microphysiological System Captures Key Features of Hepatic Insulin Resistance and Monocyte Infiltration

Three-dimensional in vitro liver models are a promising means to recapitulate key aspects of human liver disease pathologies, thereby aiding therapeutic development. Spheroidal aggregates of hepatocytes, sometimes including non-parenchymal cells, are an established approach for modeling facets of metabolism and drug responses, yet these models often lack dynamic interactions with vascular and immune cells that also contribute to disease development and progression. To address this, we developed a microphysiological system (MPS) that integrates multicellular human hepatic spheroids with self-organized microvascular networks. We show extensive interaction between primary human spheroids and functional vasculature while maintaining key hepatic functions. We demonstrate the utility of this MPS by modeling an insulin resistance state through chronic exposure to disease-mimetic media conditions. This disease model displays altered hepatocyte metabolism, dysregulated vascular features, and increased inflammation state. Enabled by the functional vasculature, we further extend this disease model to capture changes in immune cell recruitment. When culturing CD14+ monocytes in our liver MPS, a subset of monocytes extravasate, localize to hepatic spheroids, and begin differentiating into CD163+ macrophages. These cells infiltrate with greater frequency in insulin resistant samples, consistent with known clinical findings. All together, this vascularized MPS model captures disease-relevant liver biology including inflammatory features.

bioengineering↗

Are ant-plant mutualisms stronger at lower latitudes? A case study using the castor plant in the Indian subcontinent

The Biotic Interactions Hypothesis (BIH) predicts that species interactions will intensify from the poles to the tropics. We studied the ant-plant defensive interaction mediated by extrafloral nectaries (EFNs) in the castor bean plant, Ricinus communis, across a [~]21{degrees} latitudinal gradient in its naturalized range in India. Among our study sites, we found that the ant-EFN mutualism in castor bean gets stronger from sub-tropical to tropical latitudes. Investment in mutualism by plants and visitation by ants increased from higher to lower latitudes. Further, latitude significantly explained ant community composition. However, contrary to the predictions of the BIH, standing herbivory increased with latitude, perhaps because plants invest less in biotic defence at higher latitudes. To our knowledge, our study is the first to test for the patterns predicted by the BIH for an ant-plant interaction in the Paleotropics. Results from our study can also help inform sustainable pest control practices for R. communis since India is the worlds largest producer of castor oil.

ecology↗

Machine learning reveals novel targets for both glioblastoma and osteosarcoma

Glioblastoma and osteosarcoma originate from the same lineage, yet patients with these two tumour types show significant differences in survival outcomes. Transcriptomic analysis comparing these tumours reveals that over 65% genes show similar expression patterns. Principal component analysis further demonstrates substantial similarities between these two tumour types, albeit with discernible differences. Deep learning analysis employing an autoencoder unveils nuanced distinctions and similarities of these two tumours at a high resolution. A classification model, leveraging gradient boosting with eXtreme Gradient Boosting (XGBoost), achieves high accuracy in distinguishing between these two tumour types. Identification of key contributors to the models performance is facilitated by SHapley Additive exPlanations (SHAP), yielding two lists of top target genes with and without considering gender. Notably, these SHAP targets tend to cluster within one or two networks of signalling pathways. Remarkably, gene expression levels of many of these SHAP targets alone can recapitulate survival differences solely based on clinical data between glioblastoma and osteosarcoma patients. Of particular interest, C2ORF72 emerges as a common target from both lists, representing an uncharacterised protein with promising potential as a novel target for diagnostic, prognostic, and therapeutic target for both glioblastoma and osteosarcoma.

genomics↗

Classical statistical methods are powerful for the identification of novel targets for the survival of breast cancer patients

Breast cancer is a leading cause of cancer-related deaths among women. The identification of survival-related target genes is critical for improving the prognosis and outcomes of breast cancer patients. Many methods have been applied to this investigation, such as bioinformatics and machine learning approaches, yet few targets identified from these approaches have been applied in clinics. Here, we present a novel approach by using classical statistical methods of Kolmogorov-Smirnov (KS) test and Jensen-Shannon (JS) divergence to analyse the survival time and gene expression data of breast cancer patients (BRCA) from The Cancer Genome Atlas (TCGA). These methods help compare the survival time distributions and differentiate patients into high and low-risk groups based on gene expression profiles. 1,124 survival-related genes were identified based on the KS test and 18 from JS divergence values. We also identified the optimal thresholds of the expression level of these target genes, which enabled the best separation of survival groups for all breast cancer patients and each subtype of breast cancer patients. These targets were further validated through bootstrapping to ensure that significant results are not due to chance. By comparing those survival targets from previous studies, we found two were novel targets, and two were consistent with previous reports. Overall, our study provides a novel approach for identifying survival targets for breast cancer patients by integrating a series of classical statistical methods, such as the KS test, JS divergence, and bootstrapping. Our approach could also be applied to identifying the survival targets for other cancer types and provide valuable insights into cancer research and clinical applications.

bioinformatics↗

Single-Cell Transcriptomics Unveils Skin Cell Specific Antifungal Immune Responses and IL-1Ra- IL-1R Immune Evasion Strategies of Emerging Fungal Pathogen Candida auris

Candida auris is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue, yet the host immune factors that regulate the skin colonization of C. auris in vivo are unknown. In this study, we employed unbiased single-cell transcriptomics of murine skin infected with C. auris to understand the cell type-specific immune response to C. auris. C. auris skin infection results in the accumulation of immune cells such as neutrophils, inflammatory monocytes, macrophages, dendritic cells, T cells, and NK cells at the site of infection. We identified fibroblasts as a major non-immune cell accumulated in the C. auris infected skin tissue. The comprehensive single-cell profiling revealed the transcriptomic signatures in cytokines, chemokines, host receptors (TLRs, C-type lectin receptors, NOD receptors), antimicrobial peptides, and immune signaling pathways in individual immune and non-immune cells during C. auris skin infection. Our analysis revealed that C. auris infection upregulates the expression of the IL-1RN gene (encoding IL-1R antagonist protein) in different cell types. We found IL-1Ra produced by macrophages during C. auris skin infection decreases the killing activity of neutrophils. Furthermore, C. auris uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense. Collectively, our single-cell RNA seq profiling identified the transcriptomic signatures in immune and non-immune cells during C. auris skin infection. Our results demonstrate the IL-1Ra and IL-1R-mediated immune evasion mechanisms employed by C. auris to persist in the skin. These results enhance our understanding of host defense and immune evasion mechanisms during C. auris skin infection and identify potential targets for novel antifungal therapeutics.

microbiology↗

Patterns of leaf, flower and fruit phenology and environmental relationships in a seasonal tropical forest in the Indian Eastern Himalaya

Tree phenology plays an important role in determining the structure and function of tropical forest communities. However, there are few long-term studies on tree phenology from South Asia. We monitored 716 trees of 54 species monthly from 2011 to 2023 for leaf flush, flowering, and fruiting in Pakke Tiger Reserve, Arunachal Pradesh, India. We examined monthly patterns in the percentage of species and trees in leaf flush, flower and fruit and characterized phenological seasonality using circular statistics. Flowering periodicity was classified using Fourier analysis and we examined the relationships between phenological activity and temperature, rainfall, solar radiation and daylength using GAMLSS. Leaf flush and flowering were moderately seasonal, peaking in the warm dry season months of March to May. Fruiting patterns and their seasonality differed among dispersal modes. At the community level and for bird-dispersed species, fruiting was bimodal and relatively aseasonal, peaking in April and October. The highly seasonal fruiting of mammal-dispersed species peaked in October, while that of mechanically-dispersed species was bimodal and concentrated in the dry season months. The majority of species (78.13%) and trees (51.17%) flowered annually. Daylength, solar radiation and minimum temperature had significant nonlinear effects on phenology. This indicated the existence of narrow ranges of optimal climatic conditions for phenology, which could be affected by climate change. Our study emphasizes the need for long-term monitoring to rigorously quantify phenological patterns, particularly in the context of rapid global change.

plant biology↗

Direct measurement of PIP2 densities in biological membranes using a peptide-based sensor

Organization and composition of the plasma membrane are important modulators of many cellular programs. Phosphatidylinositol phosphate (PIP) lipids are low abundance membrane constituents with different arrangements of phosphate groups around an inositol head group that regulate a large number of signaling pathways. Many strategies have been developed to detect and track PIP species to monitor their clustering, mobility, and interaction with binding partners. We implement a peptide-based ratiometric sensor for the detection of PI(4,5)P2 lipids in reconstituted membrane systems that permit absolute quantification of PI(4,5)P2 densities down to physiological levels. The sensor is membrane permeable and easily applicable to measurements in living cells. Application of calibrated sensors to cells expressing common mutations in the small GTPase, Ras, showed a reshaping of surface PI(4,5)P2 levels and distributions in a mutation-specific manner. The rapid implementation of this quantitative sensing strategy to cellular studies of cellular signaling, membrane organization and dynamics should be broadly applicable.

biochemistry↗

Proliferation symmetry breaking in growing tissues

Morphogenesis of developing tissues results from anisotropic growth, typically driven by polarized patterns of gene expression. Here we propose an alternative model of anisotropic growth driven by self-organized feed-back between cell polarity, mechanical pressure, and cell division rates. Specifically, cell polarity alignment can induce spontaneous symmetry breaking in proliferation, resulting from the anisotropic distribution of mechanical pressure in the tissue. We show that proliferation anisotropy can be controlled by cellular elasticity, motility and contact inhibition, thereby elucidating the design principles for anisotropic morphogenesis.

biophysics↗