Biology subjects

Panday, M.

Publications and source records attributed to Panday, M..

3 recordsLinked to original sources

bioRxiv2025

Detection and monitoring of translocation renal cell carcinoma via plasma cell-free epigenomic profiling

TFE3 translocation renal cell carcinoma (tRCC), an aggressive kidney cancer driven by TFE3 gene fusions, is frequently misdiagnosed owing to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays that detect tumor DNA via somatic mutations or copy number alterations are unsuitable for tRCC, since it often lacks recurrent genetic alterations and because fusion breakpoints are highly variable between patients. We reasoned that epigenomic profiling could more effectively detect tRCC, because the driver fusion constitutes an oncogenic transcription factor that alters gene regulation. By defining a TFE3-driven epigenomic signature in tRCC cell lines and detecting it in patient plasma using chromatin immunoprecipitation and sequencing, we distinguished tRCC from clear cell RCC (AUC=0.87) and healthy controls (AUC=0.91) at low tumor fractions (<1%). This work establishes a framework for non-invasive epigenomic detection, diagnosis and monitoring of tRCC, with implications for other mutationally quiet, fusion-driven cancers. SIGNIFICANCETranslocation renal cell carcinoma (tRCC) is an aggressive fusion-driven subtype of kidney cancer that is frequently misdiagnosed due to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays targeting DNA alterations are suboptimal for use in tRCC due to its paucity of genomic changes. We demonstrate the utility of cell-free chromatin profiling to noninvasively detect and monitor tRCC with high accuracy, a method that could have applicability to other genomically quiet cancers.

genomics↗

bioRxiv2024

Morphometric Identification of Parvalbumin-Positive Interneurons: A Data-Driven Approach

Traditionally, anatomical studies of parvalbumin-positive (PV+) labelled interneurons describe them as a homogeneous population of neurons. In contrast, recent single-cell RNAseq studies have identified multiple transcriptomically distinct categories of PV+ cells. That difference between a single anatomical category of PV+ neurons and multiple transcriptomic categories presents a problem in understanding the role of these neurons in cortical function. One gap that might contribute to this discrepancy is that PV+ morphology is typically addressed using qualitative descriptions and simple quantifications, while single-cell RNAseq studies use big data and high dimensional analyses. PV+ neurons play critical roles in the experience-dependent development of the cortex and are often involved in disease-related changes associated with neurodegenerative and neuropsychiatric disorders. Here, we developed a modern data-driven analysis pipeline to quantify PV+ morphology. We quantified 97 morphometric features from 14274 PV+ neurons and applied unsupervised clustering that identified 13 different PV+ morphologies. We extended the analysis to compare PV+ dendritic arbour patterns and cell body morphologies. Finally, we compared the morphologies of PV+ neurons with the cell body morphologies of neurons expressing various genes associated with PV+ transcriptomic cell types. This approach identified a range of PV+ morphologies similar to the number of transcriptomic categories. It also found that the PV+ morphologies have cortical area, laminar, and transcriptomic biases that might contribute to cortical function.

neuroscience↗

bioRxiv2023

Sex-Specific Development of ssRNA Virus Receptor Gene Expression in the Human Brain

Neurotropic single-stranded RNA (ssRNA) viruses can disrupt brain function, yet little is known about how host virus receptor expression develops across the human lifespan or whether these trajectories differ between females and males. We focused on postnatal development using postmortem transcriptomic data from 33 human donors (4 months-82 years; both sexes), comprising 52 cerebral hemispheres and 15 brain areas, to characterize developmental patterns of 67 host receptor genes that mediate entry of major ssRNA viral families. Using sex-specific LOESS trajectory modelling, hierarchical clustering, and sliding-window differential expression analyses, we identified multiple non-linear developmental programs governing virus receptor expression. About half of female-male gene-area trajectory pairs exhibited divergent developmental patterns. Sex differences were most pronounced in the cortex, where high-dimensional receptor expression profiles were sufficient to predict the sex of individual cases. Sex differential expression was most frequent during early childhood, coinciding with sensitive periods of cortical circuit refinement. A targeted prenatal analysis revealed that virus receptor expression was predominantly male-biased before birth, contrasting with the predominantly female-biased expression observed during the early postnatal period. Although receptors from most viral families were broadly distributed across developmental programs, a subset of sex-by-age expression clusters showed some enrichment for specific viral lineages and glial-associated cell-type signatures. Together, these findings reveal that virus receptor expression in the human brain is organized into structured, sex-biased trajectories that dynamically reorganize over development, providing the first developmental atlas of viral entry receptors in the human brain. Significance StatementMany viruses that affect the brain use host receptors to enter cells, yet it is unclear how these receptors are expressed across the human lifespan or whether their expression differs between females and males. Using human postmortem brain transcriptomic data spanning infancy to older adulthood, we show that virus receptor genes follow dynamic, sex-biased developmental trajectories, particularly in the cortex. These patterns are strongest during early childhood and are sufficient to distinguish female and male expression profiles at the individual level. Rather than acting as static entry points, virus receptors are embedded within developmental and neuroimmune programs. These findings provide a developmental framework for understanding why vulnerability to neuroinfectious disease may vary by age, brain area, and sex.

neuroscience↗