Biology subjects

Khan, W.

Publications and source records attributed to Khan, W..

10 recordsLinked to original sources

bioRxiv2026

Amino Acid Metabolic Signature Links Pediatric Environmental Enteric Dysfunction to Maternal-Fetal Growth Restriction Across Two Independent Cohorts

Environmental Enteric Dysfunction (EED) is a leading contributor to childhood stunting. Most EED literature derives from postnatal pediatric cohorts, leaving unclear how much of the metabolic signature reflects acquired intestinal pathology versus growth restriction originating earlier. We applied genome-scale metabolic modeling to explore whether metabolic features of pediatric EED overlap with those of maternal plasma proteomes associated with adverse early-life growth. Duodenal transcriptomics from the Study of Environmental Enteropathy and Malnutrition (SEEM; 52 children with EED, 24 controls) and maternal plasma proteomics from the Alliance for Maternal and Newborn Health Improvement (AMANHI; n = 2,485 pregnant women) were integrated with the Human1 model using Reaction Inclusion by Parsimony and Transcript Distribution (RIPTiDe), followed by flux sampling and Linear Discriminant Analysis, across five growth-related proxies (small-for-gestational-age, low birth weight, preterm birth, stunting, and wasting). Amino acid and nucleotide metabolism were prominent among the top discriminating reactions in EED and most proxies. Of the 50 reactions distinguishing EED from control, 24 (48%) were among the top reactions in at least one proxy, and 19 (38%) with low birth weight, the largest of any proxy. These exploratory findings suggest shared metabolic pathways across tissues and life stages and motivate longitudinal studies.

systems biology↗

bioRxiv2026

Weight loss increases adipose dendritic cells, non-classical antigen presenting proteins, and cytotoxic effector cells

Weight cycling (i.e. cycles of weight gain, loss, and regain) is a growing health concern that has been shown to worsen risk of diabetes beyond that of obesity. Dendritic cells play a causal role in obesity-associated inflammation and metabolic disease. However, whether dendritic cells are impacted by weight cycling is not known. Here, we aimed to test the hypothesis that antigen presentation increases in dendritic cells with weight cycling. C57Bl/6J male mice were put on nutrient-matched low-fat or high-fat diets to elicit lean, weight gain, weight loss, and weight cycled groups. Adipose tissue immune cell populations and proteins related to signal 1, 2, and 3 of antigen presentation were analyzed by single cell-RNA sequencing and flow cytometry. Total adipose tissue dendritic cells, conventional type I and II dendritic cells, and monocyte-derived dendritic cells all increased with weight loss. Regarding major histocompatibility complex (MHC) protein expression, non-classical MHCIb proteins (Qa1, Qa2 and CD1d) were also highest in the weight loss group. Dendritic cells expressing the costimulatory molecule CD86 and the cytokine TNF were highest in the weight loss group. Finally, we assessed effector immune cell populations in the adipose tissue to understand the functional role of antigen presentation. CD8+ T cells, natural killer (NK) T cells, and NK cells also increased consistently with weight loss, but showed evidence of exhaustion. In sum, weight loss, but not weight cycling expands dendritic cells, increases signals for non-classical antigen presentation, and expands CD8+ T cells, NKT cells, and NK cells in the adipose tissue.

immunology↗

bioRxiv2024

Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices

Many biomedical research projects produce large-scale datasets that may serve as resources for the research community for hypothesis generation, facilitating diverse use cases. Towards the goal of developing infrastructure to support the findability, accessibility, interoperability, and reusability (FAIR) of biomedical digital objects and maximally extracting knowledge from data, complex queries that span across data and tools from multiple resources are currently not easily possible. By utilizing existing FAIR application programming interfaces (APIs) that serve knowledge from many repositories and bioinformatics tools, different types of complex queries and workflows can be created by using these APIs together. The Playbook Workflow Builder (PWB) is a web-based platform that facilitates interactive construction of workflows by enabling users to utilize an ever-growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem. Via a user-friendly web-based user interface (UI), workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflows are provided in reports containing textual descriptions, as well as interactive and downloadable figures and tables. To demonstrate the ability of the PWB to generate meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases sieves novel targets for individual cancer patients using data from the GTEx, LINCS, Metabolomics, GlyGen, and the ExRNA Communication Consortium (ERCC) Common Fund (CF) Data Coordination Centers (DCCs). The workflows created with the PWB can be published and repurposed to tackle similar use cases using different inputs. The PWB platform is available from: https://playbook-workflow-builder.cloud/.

bioinformatics↗

bioRxiv2022

Subset-specific mitochondrial and DNA damage shapes T cell responses to fever and inflammation

Heat is a cardinal feature of inflammation. Despite temperature variability and dependence of enzymes and complexes, how heat and fever affect immune cells remains uncertain. We found that heat broadly increased inflammatory activity of CD4+ T cell subsets and decreased Treg suppressive function. Th1 cells, however, also selectively developed mitochondrial dysfunction with high levels of ROS production and DNA damage. This led Th1 cells to undergo Tp53-dependent death, which was required to minimize the accumulation of mutations in heat and inflammation. Th1 cells with similar DNA damage signatures were also detected in Crohns disease and rheumatoid arthritis. Fever and inflammation-associated heat thus selectively induce mitochondrial stress and DNA damage in activated Th1 cells that requires p53 to maintain genomic integrity of the T cell repertoire. One Sentence SummaryFever temperatures augment CD4+ T cell-mediated inflammation but induce differential metabolic stress and DNA damage in T cell subsets, with Th1 cells selectively sensitive and dependent on p53 to induce apoptosis and maintain genomic integrity.

immunology↗

bioRxiv2022

Comparison of Two Individual Identification Algorithms for Snow Leopards (Panthera uncia) after Automated Detection

1. Photo-identification of individual snow leopards (Panthera uncia) is the primary technique for density estimation for the species. A high volume of images from multiple projects, combined with pre-existing historical catalogs, has made identifying snow leopard individuals within the images cost- and time-intensive. 2. To speed the classification among a high volume of photographs, we trained and evaluated image classification methods for PIE v2 (a triplet loss network), and we compared PIEs accuracy to the HotSpotter algorithm (a SIFT based algorithm). Analyzed data were collected from a curated catalog of free-ranging snow leopards photographed across years (2012-2019) in Afghanistan and from samples in captivity provided by zoos from Finland, Sweden, Germany, and the United States. 3. Results show that PIE outperforms HotSpotter. We also found weaknesses in the initial PIE model, like a minor amount of background matching, which was addressed, although likely not fully resolved, by applying background subtraction (BGS) and left-right mirroring (LR) methods. The PIE BGS LR model combined with Hotspotter showed a Rank-1: 85%, Rank-5: 95%, Rank-20: 99%. 4. Overall, our results recommend implementing PIE v2 simultaneously with HotSpotter on Whiskerbook.org.

bioinformatics↗

bioRxiv2021

Sensing Local Field Potentials with a Directional and Scalable Depth Array: DISC

A variety of electrophysiology tools are available to the neurosurgeon for diagnosis, functional therapy, and neural prosthetics. However, no tool can currently address these three critical needs: (i) access to all cortical regions in a minimally invasive manner; (ii) recordings with microscale, mesoscale, and macroscale resolutions simultaneously; and (iii) access to spatially distant multiple brain regions that constitute distributed cognitive networks. We present a novel device for recording local field potentials (LFPs) with the form factor of a stereo-electroencephalographic electrode but combined with radially positioned microelectrodes and using the lead body to shield LFP sources, enabling directional sensitivity and scalability, referred to as the DISC array. As predicted by our electro-quasistatic models, DISC demonstrated significantly improved signal-to-noise ratio, directional sensitivity, and decoding accuracy from rat barrel cortex recordings during whisker stimulation. Critically, DISC demonstrated equivalent fidelity to conventional electrodes at the macroscale and uniquely, revealed stereoscopic information about current source density. Directional sensitivity of LFPs may significantly improve brain-computer interfaces and many diagnostic procedures, including epilepsy foci detection and deep brain targeting.

bioengineering↗

bioRxiv2020

SARS-CoV-2 genome analysis of strains in Pakistan reveals GH, S and L clade strains at the start of the pandemic

ObjectivesPakistan has a high infectious disease burden with about 265,000 reported cases of COVID-19. We investigated the genomic diversity of SARS-CoV-2 strains and present the first data on viruses circulating in the country. MethodsWe performed whole-genome sequencing and data analysis of SARS-CoV-2 eleven strains isolated in March and May. ResultsStrains from travelers clustered with those from China, Saudi Arabia, India, USA and Australia. Five of eight SARS-CoV-2 strains were GH clade with Spike glycoprotein D614G, Ns3 gene Q57H, and RNA dependent RNA polymerase (RdRp) P4715L mutations. Two were S (ORF8 L84S and N S202N) and three were L clade and one was an I clade strain. One GH and one L strain each displayed Orf1ab L3606F indicating further evolutionary transitions. ConclusionsThis data reveals SARS-CoV-2 strains of L, G, S and I have been circulating in Pakistan from March, at the start of the pandemic. It indicates viral diversity regarding infection in this populous region. Continuing molecular genomic surveillance of SARS-CoV-2 in the context of disease severity will be important to understand virus transmission patterns and host related determinants of COVID-19 in Pakistan.

genomics↗

bioRxiv2019

The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer’s disease

The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimers disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region, with different subdivisions reflecting distinct connectivity profiles. However, little is understood about PMC functional connectivity and its differential vulnerability to AD pathogenesis. Using a data-driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project (HCP) to characterise the distinct functional subdivisions and unique functional-anatomic connectivity patterns of the PMC. These connectivity profiles were subsequently quantified in the Alzheimers Disease Neuroimaging Initiative (ADNI) study, to examine functional connectivity differences in (1) AD patients and cognitively normal (CN) participants and (2) the entire AD pathological spectrum, ranging from CN participants and participants with subjective memory complaints (SMC), through to those with mild cognitive impairment (MCI), and finally, patients diagnosed with AD. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex, and the central precuneus in AD patients compared to CN participants. Functional abnormalities in these subdivisions were also related to high amyloid burden and lower hippocampal volumes. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease progression and specific deficits in memory and executive function. These findings provide new evidence showing that specific vulnerabilities in PMC functional connectivity are associated with large-scale network disruptions in AD and that these patterns may be useful for elucidating potential biomarkers for measuring disease progression in future work.

neuroscience↗

bioRxiv2017

Comparative Transcriptomics of Mango (Mangifera indica L.) Cultivars Provide Insights of Biochemical Pathways Involved in Flavor and Color

Mango is an economically important fruit crop of many tropical and subtropical countries. Recently, leaf and fruit transcriptomes of mango cultivars grown in different geographical regions have characterized. Here, we presented comparative transcriptome analysis of four mango cultivars i.e. cv. Langra, cv. Zill, cv. Shelly and cv. Kent from Pakistan, China, Israel and Mexico respectively. De-novo sequence assembly generated 30,953-85,036 unigenes from RNASeq datasets of mango cultivars. KEGG pathway mapping of mango unigenes identified terpenoids, flavonoids and carotenoids biosynthetic pathways involved in flavor and color. The analysis revealed linalool as major monoterpenoid found in all cultivars studied whereas, monoterpene -terpineol was specifically found in cv. Shelly. Ditepene gibberellin biosynthesis pathway was found in all cultivars whereas, homoterpene synthase involved in biosynthesis of 4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT; an insect induced diterpene) was found in cv. Kent. Among sesquiterpenes and triterpenes, biosynthetic pathway of Germacrene-D, an antibacterial and anti-insecticidal metabolite was found in cv. Zill and cv. Shelly. Two bioactive triterpenes, lupeol and {beta}-amyrin were found in cv. Langra and cv. Zill. Unigenes involved in biosynthesis of carotenoids, {beta}-carotene and lycopene, were found in cultivars studied. Many unigenes involved in flavonoid biosynthesis were also found. Comparative transcriptomics revealed naringenin (an anti-inflammatory and antioxidant metabolite) as central flavanone responsible for biosynthesis of an array of flavonoids. The present study provided insights on genetic resources responsible for flavor and color of mango fruit.

bioinformatics↗

bioRxiv2017

The eIF2α Kinase Heme Regulated Inhibitor (HRI) Protects The Host From Infection By Regulating Intracellular Pathogen Trafficking

Phosphorylation of eIF2 by its kinases is a stress response universally conserved among the eukaryota. Previously, we reported that the eIF2 kinases Heme Regulator Inhibitor (HRI) and Protein Kinase R (PKR) control distinct activities of diverse bacterial pathogens. Specifically for Listeria monocytogenes, it was shown that in HRI-deficient cells there was a reduction in the translocation of the pathogen to the cytosolic compartment as well as reduced loading of pathogen-derived antigens on MHC-1 complexes. Here we show that Hri -/- mice, as well as wild-type mice treated with a HRI inhibitor, are more susceptible to listeriosis. In the first few hours of L. monocytogenes infection, Hri -/- mice supported greater pathogen proliferation in the liver compared to that observed in Hri +/+ mice. This greater susceptibility of Hri -/- mice was not due to deficits in immune cell development as proportions and numbers of innate and adaptive cell compartments were largely normal and these mice could mount potent antibody responses to a model T cell-dependent antigen. Using in vitro cellular infection assays, we show that the rate of pathogen efflux from infected Hri -/- macrophages and fibroblasts is significantly higher than that observed in infected Hri +/+ cells. In contrast to the stark differences between Hri +/+ and Hri -/- cells in the infection dynamics of virulent L. monocytogenes, HRI was entirely dispensable for killing non-virulent strains of L. monocytogenes. These results suggest that in wild-type cells, HRI helps ensure the cellular confinement of virulent L. monocytogenes and loading of cytosolic-derived antigens on MHC-1 complexes that limit pathogen spreading and activating innate immune responses, respectively.

immunology↗