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Biology subjects

Singhvi, S.

Publications and source records attributed to Singhvi, S..

4 recordsLinked to original sources

When Color Adds Nothing: A Causal Audit of Channel Triplication in Alzheimer's MRI Classification

Medical imaging pipelines routinely copy single-channel grayscale data into three identical RGB channels before classification, usually without justification. This study tests whether that step affects model predictions. Four coordinated experiments on bit-identical RGB inputs sorted eleven classical machine learning models into three groups: five that were invariant to the copy, two that were nearly invariant, and four whose predictions changed. On the Kaggle Alzheimer MRI Dataset (6,400 images, four classes, five seeds), five models (AdaBoost, HistGradientBoosting, KNN, SVM_Polynomial, and SVM_RBF) produced identical predictions in both conditions for every seed, where KNN is k-nearest neighbors and SVM a support vector machine, with polynomial and radial basis function (RBF) kernels. Two models (GaussianNB and SVM_Linear) differed by at most one of 1,280 samples, a dataset-dependent gap rather than exact invariance. The remaining four (DecisionTree, ExtraTrees, RandomForest, and LogisticRegression) differed substantively. A regularization sweep on Logistic Regression traced its gap to a single cause. As L2 regularization weakened, the color-minus-grayscale macro F1 gap shrank steadily, from +12.07 percentage points at C=0.001 to near zero at C=100 (paired Wilcoxon p=0.0020 under strong regularization), showing the effect scales with feature count rather than image content. A replication on the OASIS dataset, matched in size and class balance, reproduced every grouping, and the Logistic Regression gap reappeared in the same direction at smaller magnitude (+5.30 points macro F1). Two deep networks, ResNet18 and DenseNet121, gave identical predictions across all twenty paired conditions. Channel triplication left most models unchanged while multiplying classical training time 2.3 to 4.0 times without benefit.

bioengineering↗

Decoding Diabetes: Harnessing AI to Accurately Predict Real-Time and Future Blood Glucose Levels for Diabetes Management Using Diet, Exercise, Insulin Intake, and Heart Rate Variability

Continuous glucose monitoring (CGM) systems play a crucial role in diabetes care. Yet, they focus solely on blood glucose levels (BGL), neglect diet, exercise, and medication, and lack predictive capabilities, leaving patients and clinicians with reactive rather than proactive solutions. This study introduces Dual Temporal Recurrent Ensemble (DTRE), a novel AI model that bridges these gaps by enabling real-time BGL monitoring without a traditional CGM and forecasting BGL for 30 to 120 minutes into the future when integrated with CGM data. The models performance is based on two parallel branches of hybrid models that combine advanced machine learning architectures for accurate predictions and integrate key biomarkers like diet, exercise, insulin intake, heart rate (HR), and heart rate variability (HRV). This pioneering study developed and validated DTRE on two diverse datasets, OHIOT1DM and D1NAMO, achieving exceptional forecasting accuracy: a Mean Absolute Relative Difference (MARD) of 7.6% at 30 minutes and 19.2% at 120 minutes, outperforming existing models by 13 to 41%. DTRE also surpassed commercial CGM systems for real-time BGL predictions by achieving a MARD of 7.17% on the high-frequency D1NAMO dataset compared to FreeStyle Libre 3 (7.9%) and Dexcom G7 (8.2%). DTRE is the first AI-driven virtual BGM (vBGM) to integrate all four pillars of diabetes care and validate them on two diverse datasets. It offers a non-invasive, low-cost, and proactive solution. Its real-time insights can provide patients and clinicians with actionable data, transforming diabetes management for individuals who depend on insulin. Validation across diverse datasets underscores its potential for global application. Human Subject Research StatementThis research did not utilize any human subjects. Pre-existing and published databases were used for this research.

bioinformatics↗

Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains

Mycobacterium abscessus (Mab) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in Mab have been primarily performed on reference strains. Given the growing public health threat of Mab infections, understanding the functional genomic differences among Mab clinical isolates can provide more insight into how its genetic diversity influences gene essentiality, clinically relevant phenotypes, and importantly, potential drug targets. To determine the functional genomic diversity among Mab strains, we conducted transposon-sequencing (TnSeq) on 21 genetically diverse clinical isolates, including 15 M. abscessus subsp. abscessus isolates and 6 M. abscessus subsp. massiliense isolates, cataloging all the essential and non-essential genes in each strain. Pan-genome analysis revealed a core set of 3845 genes and a large accessory genome of 11,507. We identified 259 core essential genes across the 21 clinical isolates and 425 differentially required genes, representing [~]10% of the Mab core genome. We also identified genes whose requirements were sub-species, lineage, and isolate-specific. Finally, by correlating TnSeq profiles, we identified 19 previously uncharacterized genetic networks in Mab. Altogether, we find that Mab clinical isolates are not only genetically diverse but functionally diverse as well.

microbiology↗

High-density transposon mutagenesis in Mycobacterium abscessus identifies an essential penicillin-binding lipo-protein (PBP-lipo) involved in septal peptidoglycan synthesis and antibiotic sensitivity

Mycobacterium abscessus (Mab) is a rapidly growing non-tuberculous mycobacterium (NTM) that causes a wide range of infections. Treatment of Mab infections is difficult because the bacterium is intrinsically resistant to many classes of antibiotics. Developing new and effective treatments against Mab requires a better understanding of the unique vulnerabilities that can be targeted for future drug development. To achieve this, we identified essential genes in Mab by conducting transposon-sequencing (TnSeq) on the reference Mab strain ATCC 19977. We generated [~]51,000 unique transposon mutants and used this high-density library to identify 362 essential genes for in vitro growth. To investigate species-specific vulnerabilities in Mab, we further characterized MAB_3167c, a predicted penicillin-binding-lipoprotein (PBP-lipo) that is essential in Mab and non-essential in Mycobacterium tuberculosis (Mtb). We found that PBP-lipo primarily localizes to the subpolar region and later to the septum as cells prepare to divide. Depletion of Mab PBP-lipo causes cells to elongate, develop ectopic branches, and form multiple septa. Knockdown of PBP-lipo along with PbpB, DacB1, and a carboxypeptidase, MAB_0519 lead to synergistic growth arrest. In contrast, these genetic interactions were absent in the Mtb model organism, Mycobacterium smegmatis, indicating that the PBP-lipo homologs in the two species exist in distinct genetic networks. Finally, repressing PBP-lipo sensitized the reference strain and 11 Mab clinical isolates to several classes of antibiotics, including the {beta}-lactams, ampicillin and amoxicillin by greater than 128-fold. Altogether, this study presents PBP-lipo as a key enzyme to study Mab specific processes in cell wall synthesis and importantly positions PBP-lipo as an attractive drug target to treat Mab infections.

microbiology↗