Biology subjects

Mirchandani, C. D.

Publications and source records attributed to Mirchandani, C. D..

4 recordsLinked to original sources

bioRxiv2025

Wolbachia induces host cell identity changes and determines symbiotic fate in Drosophila

Host-associated bacteria influence eukaryotic cellular differentiation, but the underlying mechanisms are difficult to disentangle because of cell-type-specific tropisms and phenotypes. The association between Wolbachia pipientis and Drosophila melanogaster offers a tractable system for gaining high-resolution insight into how host and microbe gene expression interact. Using Wolbachia-infected D. melanogaster cell lines, we show that the native wMel strain alters host phenotypic, transcriptomic, and chromatin conformation states. High-throughput imaging reveals that wMel infection differentially alters host cellular phenotypes in a titer-independent manner in some cell lines. These phenotypically altered host cells exhibit differential gene expression complementary to the expression patterns observed in their wMel symbionts. Infection was also negatively associated with chromatin organization and histone modification pathways, prompting us to investigate differences in chromatin conformation between infection states. Micro-C chromatin contact data reveal that wMel infection conferred increased D. melanogaster chromatin contacts coinciding with both increased compartmentalization and derepression. The X chromosome exhibited evidence consistent with altered dosage compensation, with no downstream alteration of the X:autosome transcript ratio or X-linked histone acetylation, consistent with a dosage compensation-mediated male-killing mechanism encoded by wMel that has been suppressed in D. melanogaster. Overall, these findings suggest that the character of Wolbachia symbiosis, cooperative or antagonistic, emerges in response to the host cellular environment. Furthermore, these results demonstrate that in vitro cell lines offer promising avenues for uncovering the functional genetic basis of microbe-induced host phenotypes.

cell biology↗

bioRxiv2025

Efficient Estimation of Nucleotide Diversity and Divergence using Depth Information

The increasing scale of population genomic datasets presents computational challenges in estimating summary statistics such as nucleotide diversity ({pi}) and divergence (dxy). Unbiased estimates of diversity require knowledge of missing data and existing tools require all-sites VCFs. However, generating these files is computationally expensive for large datasets. Here, we introduce Callable Loci And More (clam), a tool that leverages callable loci--determined from depth information--to estimate population genetic statistics using a variant-only VCF. This approach offers improvements in storage footprint and computational performance compared to contemporary methods. We benchmark clam using a large muskox dataset and demonstrate that it produces unbiased estimates of {pi} while reducing runtime and storage requirements, compared to an existing approach. clam provides an efficient and scalable alternative for population genomic analyses, facilitating the study of increasingly large and diverse datasets. clam is available as a standalone program and integrated into snpArcher for efficient reproducible population genomic analysis.

genomics↗

bioRxiv2024

Limited genomic signatures of population collapse in the critically endangered black abalone (Haliotis cracherodii)

The black abalone, Haliotis cracherodii, is a large, long-lived marine mollusc that inhabits rocky intertidal habitats along the coast of California and Mexico. In 1985, populations were impacted by a bacterial disease known as withering syndrome (WS) that wiped out >90% of individuals, leading to the species designation as critically endangered. Current conservation strategies include restoring diminished populations by translocating healthy individuals. However, population collapse on this scale may have dramatically lowered genetic diversity and strengthened geographic differentiation, making translocation-based recovery contentious. Additionally, the current prevalence of WS is unknown. To address these uncertainties, we sequenced and analyzed the genomes of 133 black abalone individuals from across their present range. We observed no spatial genetic structure among black abalone, with the exception of a single chromosomal inversion that increases in frequency with latitude. Genetic divergence between sites is minimal, and does not scale with either geographic distance or environmental dissimilarity. Genetic diversity appears uniformly high across the range. Despite this, however, demographic inference confirms a severe population bottleneck beginning around the time of WS onset, highlighting the temporal offset that may occur between a population collapse and its potential impact on genetic diversity. Finally, we find the bacterial agent of WS is equally present across the sampled range, but only in 10% of individuals. The lack of genetic structure, uniform diversity, and prevalence of WS bacteria indicates that translocation could be a valid and low-risk means of population restoration for black abalone species recovery.

evolutionary biology↗

bioRxiv2023

A fast, reproducible, high-throughput variant calling workflow for evolutionary, ecological, and conservation genomics

The increasing availability of genomic resequencing datasets and high quality reference genomes across the tree of life present exciting opportunities for comparative population genomic studies. However, substantial challenges prevent the simple reuse of data across different studies and species, arising from variability in variant calling pipelines, data quality, and the need for computationally intensive reanalysis. Here, we present snpArcher, a flexible and highly efficient workflow designed for the analysis of genomic resequencing data in non-model organisms. snpArcher provides a standardized variant calling pipeline and includes modules for variant quality control, data visualization, variant filtering, and other downstream analysis.Implemented in Snakemake, snpArcher is user-friendly, reproducible, and designed to be compatible with HPC clusters and cloud environments. To demonstrate the flexibility of this pipeline, we applied snpArcher to 26 public resequencing datasets from non-mammalian vertebrates. These variant datasets are hosted publicly to enable future comparative population genomic analyses. With its extensibility and the availability of public datasets, snpArcher will contribute to a broader understanding of genetic variation across species by facilitating rapid use and reuse of large genomic datasets.

genomics↗