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Bharti, S.

Publications and source records attributed to Bharti, S..

7 recordsLinked to original sources

Integrative transcriptome analysis reveals distinct and common stress-responsive regulatory networks driving drought and heat responses in sorghum

Drought and heat are key abiotic stresses that severely affect crop production. Sorghum (Sorghum bicolor L. Moench), a drought-resilient cereal, serves as a model for studying abiotic stress responses in cereals. To elucidate the molecular responses to individual drought and heat stress, we conducted a transcriptome analysis of sorghum seedlings subjected to individual drought and heat treatment for 1h and 6h. Our analysis revealed distinct as well as overlapping patterns of gene expression between the two stresses at two time points, with a larger transcriptional shift observed at 6h of drought and heat treatment. We identified 410 and 4,136 differentially expressed genes (DEGs) in response to 1 and 6 h of drought treatments, respectively, whereas 1,807 and 2,776 DEGs were identified under 1 and 6 h of heat treatments. Among all four stress conditions, 32 common DEGs were identified. Genes encoding ion transporters were enriched among DEGs common in both 1h stress treatments. Genes involved in ribosome biogenesis were enriched among the common DEGs in both 6 h stress treatments. Specifically, drought-regulated genes were involved in ribosome biogenesis, whereas heat-induced genes were involved in protein folding and histone modifications. Enrichment of ribosome biogenesis in different sets of DEGs suggests that maintaining a balance between growth and survival by regulating protein synthesis may play a role in defining early stress response in sorghum. 6h of drought resulted in strong upregulation of abscisic acid and jasmonate-associated genes. Genes encoding bZIP, MYB, and HSF transcription factors displayed both stress-specific and common temporal regulation, suggesting vital regulatory roles of these transcription factors in mediating responses to drought and heat treatments. Extensive downregulation of genes encoding core histone proteins, in response to both 6h of drought and heat stress, was detected, indicating possible roles of chromatin structure and accessibility in mediating early responses to drought and heat treatments in sorghum.

plant biology↗

mim: A lightweight auxiliary index to enable fast, parallel, gzipped FASTQ parsing

The FASTQ file format is the lingua franca of primary data distribution and processing across most of bioinformatics. Over time, the compression, storage, transmission, and decompression of gzip compressed fastq.gz files has become a substantial scalability bottleneck in the modern world of fast and massively parallel genomics tools and algorithms. In this work, we introduce mim: a lightweight, auxiliary index that enables fast, parallel, and highly-scalable parsing of compressed fastq.gz files. The creation of the mim index for a file is a one-time operation that can be performed in time comparable to that of simply decompressing and parsing the file (index creation induces [~] 20% overhead) and with minimal working memory. The mim index itself is very small, usually about [Formula]th of the size of the original compressed file, and can be easily stored along side the file or fetched from a remote location when it is needed. Further, the mim index is purely additive -- it does not modify the original gzipped FASTQ file in any way, nor require that the file be recompressed or rewritten -- and thus it does not require converting the massive back catalog of existing raw sequencing data. To demonstrate the feasibility and utility of the mim index, we benchmark construction of the mim index on a variety of existing gzipped FASTQ data, and also measure thread-scaling of mim index-assisted parallel FASTQ parsing on a simple parsing/ decompression-related task. We find that, for the one-time cost of index creation, and a small fraction of extra storage space, the mim index can massively accelerate the ingestion and parsing of gzipped FASTQ data, exhibiting near linear thread scaling in our experiments. mim is written in C++17, and is available as open source software under a BSD 3-clause license at https://github.com/COMBINE-lab/mim.

bioinformatics↗

Structural Validation of the Intermediate Leptomeningeal Layer in the Human Central Nervous System

Traditionally, the human central nervous system (CNS) is described as having three meningeal layers, from outer to inner: dura mater, arachnoid mater, and pia mater. The arachnoid and pia mater are called the leptomeninges, and the space between them is filled with cerebrospinal fluid (CSF). Using gross dissection, light microscopy, and ultrastructural analysis of fresh postmortem and cadaveric CNS specimens spanning fetal to adult ages (N=61), we demonstrate a fibrocellular intermediate leptomeningeal layer (ILL) from the cortex to the caudal end of the spinal cord. The ILL divides the subarachnoid space (SAS) into two distinct structural compartments, through which vessels and nerves pass. The ILL shows unique structural features, such as dips into the brains sulci and fissures, as a double-fold membrane that bears intra-layer trabeculae, carries vessels, and forms the perivascular sheath. Moreover, throughout the CNS, it appears to be a non-sieved barrier, characterized by the presence of tight and adherens junctions. ILL, predominantly in the spinal cord, contains macrophage-like cells, indicating its layer-specific immune properties. The ILL warrants recognition as a distinct human meningeal layer with potential barrier and immune functions. SignificanceO_ST_ABSAn Intermediate Leptomeningeal Layer encloses the Central Nervous System in HumansC_ST_ABSThe integrated analysis of our macroscopic, microscopic, and ultrastructural study provides robust support for an intermediate leptomeningeal layer (ILL) in the subarachnoid space (SAS) of the human central nervous system (CNS) along the entire neural axis. The ILL is a fibrocellular macroscopic structure, with restricted permeability, that divides the cerebrospinal fluid (CSF)-filled SAS into two distinct structural compartments. Uniquely, ILL revealed the presence of cells with macrophage-like properties, suggesting a possible role in immune surveillance. The ILL may redefine the established concept of protective coverings of CNS, CSF circulation dynamics, and the role of leptomeninges in health and disease, including drug delivery.

neuroscience↗

Conservation and discovery of regulatory motifs across oomycetes through comparative genomic analysis

Promoter sequences contain specific transcription factor (TFs) binding sites that regulate gene expression. While the conservation of TFs in pathogen development and infection among oomycetes is known, little is understood about TFs bind to conserved promoter regions across species. This study employs a robust comparative computational genomics approach to identify the TFs binding to orthologous DNA motifs in oomycetes. By integrating high-confidence TF binding site (TFBS) profiles, in-silico motif discovery, sequence conservation analysis and protein sequence similarity searches, the study revealed conserved regulatory mechanisms in oomycetes. The multi-layered computational framework identified two major TF classes in oomycetes: Cys2-His2 (C2H2) zinc finger proteins and winged helix repressor proteins, binding to orthologous motifs regulating gene clusters involved in epigenetic regulation, effectors, intracellular trafficking, host cell wall degrading enzymes, RNA processing and cytoskeletal organization. Structural comparisons indicate high sequence similarity between oomycete TFs and well-characterized eukaryotic TFs, supporting the predictive power of the computational approach. Moreover, motif plasticity analysis across developmental phases revealed conserved and phase-specific motifs emphasizing dynamic transcriptional regulation during infection and colonization. The presence of highly conserved motifs across multiple oomycete species suggests strong evolutionary selection pressure on key regulatory elements. The results provide a computational foundation for future experimental validation, guiding functional characterization of transcriptional regulation in oomycetes. This study highlights the potential of in-silico TFBS discovery for understanding gene regulation, paving the way for targeted experimental approaches such as ChIP-seq or electrophoretic mobility shift assays (EMSA).

bioinformatics↗

A single-cell transcriptome atlas of adult male and female human hookworm Ancylostoma ceylanicum

Hookworms infect over 500 million people globally and represent a major neglected tropical disease. The prevalence, high reinfection rate, limited drugs and emerging resistance underscore the need for new therapeutic or vaccine targets. To mitigate halted progress of discovering targets, we provide new molecular insights into sex-specific expression and cellular heterogeneity by generating the first single-cell atlas of male and female transcriptome for the human hookworm Ancylostoma ceylanicum. We systemically annotated 10 transcriptionally distinct cell types in female and 13 in male hookworm by comparing marker genes with tissue-specific knowledge. Non-reproductive tissues included pharynx, intestine, cephalic and pharyngeal glands, muscle and hypodermis, complemented with female reproductive tissues (ovary, uterus, eggs, seminal receptacle), and male reproductive tissues (testis, seminal vesicle, cement gland, sperm). Anatomical confocal microscopy and fluorescence in situ hybridization assisted in visualizing these tissues and confirming marker genes. Functional comparisons revealed previously undescribed tissue pathways and molecular markers, providing previously unrecognized insights into hookworm biology, and new targets. Overall, this study presents a detailed cell-type atlas for adult stages of this important yet neglected metazoan parasite. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/631133v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@ed5de0org.highwire.dtl.DTLVardef@1ae2bf6org.highwire.dtl.DTLVardef@1c835c6org.highwire.dtl.DTLVardef@1429bb4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

sMAP: An interactive microarray data analysis tool for early-stage researchers

Microarray data enables biologists to extract differentially expressed genes (DEGs) across multiple phenotypes. While several pipelines and tools exist to perform microarray data analysis, they are targeted to users with moderate to advanced computational understanding and lack an easy-to-use, interactive and dynamic methodology to perform analysis assisted with comprehensive learning resources. In this study, we developed an interactive application "sMAP" (Standard Microarray Analysis Pipeline) to make transcriptome microarray data analysis more accessible in learning environments and to enable the identification of significant pathological biomarkers. In a case study of colorectal cancer, we showed that sMAP enabled us to reproduce previous findings and discover relevant pathways. sMAP provides a comprehensive set of tutorials and learning documentation to help early-stage researchers. The latest URLs of sMAPs hosting, tutorial, and frequently updated documentation can be found at https://github.com/BI-STEM-Away/sMAP.

bioinformatics↗