Biology subjects

Chadha, A.

Publications and source records attributed to Chadha, A..

8 recordsLinked to original sources

bioRxiv2026

A Conversational Multi-Agent AI System for Integrated Multi-Omics Analysis and Biomedical Discovery

Single-cell and spatial omics offer unprecedented opportunities to decipher the mechanisms of disease, however, this process requires teams of experts, iterative trial-and-error and reasoning across modalities. Here we present LungChat (https://chat.lungmap.net), a conversational system for integrated multi-omics analysis and biomedical discovery, deployed as a hierarchical multi-agent architecture in which a supervisor decomposes natural-language questions into parallel, tool-grounded tasks spanning single-cell and spatial analyses, literature and clinical-trial synthesis, and drug repurposing. To predict new therapeutics, LungChat implements Direction-Aware Repurposing and Targeting (DART) to distinguish perturbations that reverse disease transcriptional programs from those that reinforce them, at the cell-type level, for safety prediction. Controlled architecture ablations showed that hierarchical orchestration improved grounded abstention and token efficiency and preserved strong performance on complex multi-step tasks. In pulmonary disease case studies, LungChat independently prioritized saracatinib for IPF through drug-connectivity screening, followed by DART-based cell-type analysis; the same compound has been evaluated in the STOP-IPF clinical trial (NCT04598919). The system also recovered fluticasone propionate, an established COPD therapy, through a single orchestrated analysis. This tissue-agnostic system provides a blueprint for verifiable agentic AI systems that support reproducible scientific discovery.

bioinformatics↗

bioRxiv2026

GROQ-seq Datasets Across Transcription Factors (LacI, RamR, VanR), T7 RNA Polymerase and TEV Protease

Predicting any proteins function from its sequence alone would be a significant breakthrough in molecular biology. Although machine learning approaches have sought to tackle this, their limited generalizability reflects the absence of sufficiently large, open, diverse, and unified datasets. To address this data gap, we developed a high-throughput experimental platform called GROQ-seq (Growth-based Quantitative Sequencing). In GROQ-seq, a proteins function can be linked to a sequencing-based readout that enables scalable characterization of large variant libraries in Escherichia coli. Here, we present pilot datasets demonstrating its performance across three distinct protein function classes: transcription factors, polymerases, and proteases. The objective of this report is to present the datasets and to provide users with a clear and transparent characterization of their properties, including both the strengths and limitations.

bioengineering↗

bioRxiv2025

Modeling Oxidative Stress-Linked Telogen Effluvium: A Monte Carlo Simulation Using Published Trichoscopy Norms and Cannabis Exposure Distributions

Cannabis exposure has increased with greater legalization, yet little is known about cannabis and its possibly relevant impacts on hair biology. The literature suggests that inhalative byproducts and endocannabinoid signaling can affect processes that may affect anagen stability, and, as hair follicles are metabolically active organs susceptible to oxidative and inflammatory damage, they could be affected as well. Therefore, this study intends to understand whether population-based cannabis exposure behaviors statistically correlate with symptoms characteristic of diffuse shedding when applied to a virtual population. A synthetic dataset of 140 individuals was generated using a Monte Carlo framework parameterized by published trichoscopy-based follicular density values, national cannabis use statistics, and psychometric properties reported for hair loss and dermatologic quality of life measures. Cannabis exposure, density, and SAHL scores were sampled from probability distributions specified by published means, standard deviations, and plausible covariance structures rather than from individual-level patient data. The simulated dataset was then subjected to Pearson correlations, linear regression, and ANCOVA with demographic covariates. Higher cannabis exposure was associated with increased SAHL severity (r = 0.31, p < 0.01) and reduced follicular density (r = -0.38, p < 0.05). Both associations remained statistically significant after covariate adjustment, and female-assigned profiles showed larger effect magnitudes. These associations reflect patterns in the modeled population structure rather than clinical observations, but they parallel mechanistic pathways described in oxidative stress and hair cycle research. As a simulation study, these results cannot establish causality and are limited by underlying assumptions in the source distributions. However, they demonstrate that publicly available data and computational modeling can be combined to generate preliminary hypotheses about how cannabis exposure patterns may align with characteristics observed in telogen effluvium. Future work should integrate empirical biomarkers, longitudinal imaging, and clinical datasets to determine whether these modeled patterns correspond to measurable biological effects.

bioinformatics↗

bioRxiv2024

Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking

Calibrated transcriptional outputs in cellular signaling require fine regulation of transcription factor activity. In vertebrate Hedgehog (Hh) signaling, the precise output of the final effectors, the GLI (Glioma-associated-oncogene) transcription factors, depends on the primary cilium. In particular, the formation of the activator form of GLI upon pathway initiation requires its concentration at the distal cilium tip. However, the mechanisms underlying this critical step in Hh signaling are unclear. We developed a real-time imaging assay to visualize GLI2, the primary GLI activator isoform, at single particle resolution within the cilium. We observed that GLI2 is a cargo of Intraflagellar Transport (IFT) machinery and is transported with anterograde bias during a restricted time window following pathway activation. Our findings position IFT as a crucial mediator of transcription factor transport within the cilium for vertebrate Hh signaling, in addition to IFTs well-established role in ciliogenesis. Surprisingly, a conserved Hh pathway regulator, the atypical non-motile kinesin KIF7, is critical for the temporal control of GLI2 transport by IFT and the spatial control of GLI2 localization at the cilium tip. This discovery underscores the collaborative role of a motile and a non-motile cilium-specific cytoskeletal system in determining the transcriptional output during Hh signaling.

cell biology↗

bioRxiv2024

Legionella uses host Rab GTPases and BAP31 to create a unique ER niche

Upon entry into host cells, the facultative intracellular bacterium Legionella pneumophila (L.p.) uses its type IV secretion system, Dot/Icm, to secrete ~330 bacterial effector proteins into the host cell. Some of these effectors hijack endoplasmic reticulum (ER)-derived vesicles to form the Legionella-containing vacuole (LCV). Despite extensive investigation over decades, the fundamental question persists: Is the LCV membrane distinct from or contiguous with the host ER network? Here, we employ advanced photobleaching techniques, revealing a temporal acquisition of both smooth and rough ER (sER and rER) markers on the LCV. In the early stages of infection, the sER intimately associates with the LCV. Remarkably, as the infection progresses, the LCV evolves into a distinct niche comprising an rER membrane that is independent of the host ER network. We discover that the L.p. effector LidA binds to and recruits two host proteins of the Rab superfamily, Rab10, and Rab4, that play significant roles in acquiring sER and rER membranes, respectively. Additionally, we identify the pivotal role of a host ER-resident protein, BAP31, in orchestrating the transition from sER to rER. While previously recognized for shuttling between sER and rER, we demonstrate BAP31s role as a Rab effector, mediating communication between these ER sub-compartments. Furthermore, using genomic deletion strains, we uncover a novel L.p. effector, Lpg1152, essential for recruiting BAP31 to the LCV and facilitating its transition from sER to rER. Depletion of BAP31 or infection with an isogenic L.p. strain lacking Lpg1152 results in a growth defect. Collectively, our findings illuminate the intricate interplay between molecular players from both host and pathogen, elucidating how L.p. orchestrates the transformation of its residing vacuole membrane from a host-associated sER to a distinct rER membrane that is not contiguous with the host ER network.

cell biology↗

bioRxiv2023

A novel subset of colonocytes targeted by Citrobacter rodentium elicits epithelial MHCII-restricted help from CD4 T cells

Interleukin (IL)-22 plays a non-redundant role in immune defense of the intestinal barrier1-3. We recently discovered an indispensable role for T cells, but not ILCs, in sustaining IL-22 signaling required for protection of colonic crypts against invasion during infection by the enteropathogen, Citrobacter rodentium (C.r)4. However, identification of the intestinal epithelial cell (IEC) subsets targeted by T cell-derived IL-22 and how T cell-derived IL-22 sustains activation in IECs are undefined. Here, we identify a novel subset of absorptive IECs in the mid-distal colon that are differentially targeted by C.r and are differentially responsive to IL-22 signaling. Importantly, MHCII expression by these colonocytes was required to elicit T cell-activated IL-22 signaling necessary to resist C.r invasion. Our findings explain the basis for the regionalization of the host response to C.r and demonstrate that epithelial cells must elicit MHCII-dependent help from IL-22-producing T cells to orchestrate immune protection in the intestines.

immunology↗

bioRxiv2022

helixCAM: A Platform for Programmable Cellular Assembly in Bacteria and Human Cells

Interactions between cells are indispensable for creating structure and signaling. The ability to direct precise cell-cell interactions would be powerful for engineering tissues, understanding signaling pathways, and directing immune cell targeting. In humans, intercellular interactions are mediated by cell adhesion molecules (CAMs). However, CAMs are natively expressed by many cells and have cross-reactivity, making them unsuitable for programming specific interactions. Here, we showcase "helixCAM," a platform for engineering novel CAMs by presenting coiled-coil peptides on the cell surface. helixCAMs were able to create specific cell-cell interactions and direct patterned aggregate formation in bacteria and human cells. We built rationally designed helixCAM libraries and discovered novel high-performance helixCAM pairs. High-affinity helixCAMs were then used for multicellular engineering applications, such as spherical layering, adherent cell targeting, and surface patterning. The helixCAMs are an expandable platform for directing complex multicellular assemblies, and we foresee its utility in tissue engineering, immunology, and developmental biology.

synthetic biology↗

bioRxiv2020

Extended in vitro inactivation of SARS-CoV-2 by titanium dioxide surface coating

SARS-CoV-2 transmission occurs via airborne droplets and surface contamination. We show tiles coated with TiO2 120 days previously can inactivate SARS-CoV-2 under ambient indoor lighting with 87% reduction in titres at 1h and complete loss by 5h exposure. TiO2 coatings could be an important tool in containing SARS-CoV-2.

microbiology↗