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Biology subjects

Tripathi, D.

Publications and source records attributed to Tripathi, D..

3 recordsLinked to original sources

A Deep Learning Approach for Modelling the Complex Relationship between Environmental Factors and Biological Features

Environmental factors play a pivotal role in shaping the genetic and phenotypic diversity among organisms. Understanding the influence of the environment on a biological phenomenon is essential for deciphering the mechanisms resulting in trait differences among organisms. In this study, we present a novel approach utilizing an Artificial Neural Network (ANN) model to investigate the impact of environmental factors on a wide range of biological phenomena. Our proposed workflow includes hyperparameter optimization using model-based methods such as Bayesian and direct-search methods such as Random Search, and a new approach combining random search and linear models (RandomSearch+lm) to ensure a robust ANN architecture. Moreover, we employed a generalized version of the variable importance method to generate the feature importance metric using estimated weights from ANN. By applying this comprehensive ANN-based approach to functional genomics, we can gain valuable insights into the mechanisms underlying trait differentiation in organisms, while simultaneously enabling prediction and feature selection tasks. This methodology provides a robust and efficient framework for studying the complex relationships between environmental factors and biological features in biological systems.

genomics↗

HIV-differentiated metabolite N-Acetyl-L-Alanine dysregulates human natural killer cell responses to Mycobacterium tuberculosis infection

BackgroundMycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and causes 1.8 million deaths each year. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared to the HIV-LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. MethodsPlasma samples collected from healthy and HIV-infected individuals were investigated by liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using an online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, quantitative reverse transcription PCR (qRT-PCR) were performed by standard procedure to determine the surface markers, cytokines and other signaling molecule expression. Seahorse extra cellular flux assays were used to measure the mitochondrial oxidative phosphorylation and glycolysis. ResultsSix metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared to healthy donors. One of the HIV-upregulated metabolites, N-Acetyl-L-Alanine (ALA), inhibits pro-inflammatory cytokine IFN-{square} production by NK cells of LTBI+ individuals. ALA inhibits glycolysis of LTBI+ individuals NK cells in response to Mtb. ConclusionsOur findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV-Mtb interaction and providing the implication of nutrition intervention and therapy for HIV-Mtb co-infected patients.

immunology↗

A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

RationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5M rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 M). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5M rfhSP-D. ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.

immunology↗