PlantReg: the reconstruction of links between transcription factor regulatory networks and biological processes under their control

Vavilov Journal of Genetics and Breeding, Journal Year: 2025, Volume and Issue: 28(8), P. 950 - 959

Published: Jan. 26, 2025

The description of the path from a gene to trait, as main task many areas in biology, is currently being equipped with new methods affecting not only experimental techniques, but also analysis results. pleiotropic effect due its participation numerous biological processes involved different traits. A widespread use genome-wide sequencing transcripts and transcription factor (TF) binding regions has made following tasks relevant: unveiling effects TFs based on functions their target genes; compiling lists that regulate interest; describing ways TF functioning (their primary secondary targets, higher order interactions process under study). We have previously developed method for reconstruction regulatory networks proposed an approach allows identifying which are controlled by these how this control exerted. In paper, we implemented PlantReg, program available web service. paper describes works. input consists list genes – known or putative transcriptional regulators genes. As output, provides enriched genes, well information about through controlled. illustrated PlantReg deciphering regulation initiated at early salt stress response Arabidopsis thaliana L. With identified stimulated stress, specific sets activate each process. one (response abscisic acid) example, showed mainly affects acid signaling key regulation. Thus, convenient tool generating hypotheses molecular mechanisms plant

Language: Английский

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Spotlight on amino acid changing mutations in the JAK-STAT pathway: from disease-specific mutation to general mutation databases

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 20, 2025

The JAK-STAT pathway is central to cytokine signaling and controls normal physiology disease. Aberrant activation via mutations that change amino acids in proteins of the can result diseases. While disease-centric databases like COSMIC catalog cancer, their prevalence healthy populations remains underexplored. We systematically studied such genes by comparing population-focused All Us database. Our analysis revealed frequent all JAK STAT domains, particularly among white females. further identified three categories: Mutations uniquely found were associated with cancer literature but could not be COSMIC, underscoring COSMIC's limitations. unique underline potential as drivers due absence general population. present both databases, e.g., JAK2Val617Phe/V617F - widely recognized a driver hematopoietic cells, without disease associations Us, raising possibility combinatorial SNPs might responsible for development. These findings illustrate complementarity understanding mutation impacts underscore need multi-mutation analyses uncover genetic factors underlying complex diseases advance personalized medicine.

Language: Английский

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Data-driven projections of candidate enhancer-activating SNPs in immune regulation

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 26, 2025

Abstract Background Millions of single nucleotide polymorphisms (SNPs) have been identified in humans, but the functionality almost all SNPs remains unclear. While current research focuses primarily on altering one amino acid to another one, majority are located intergenic spaces. Some these can be found candidate cis-regulatory elements (CREs) such as promoters and enhancers, potentially destroying or creating DNA-binding motifs for transcription factors (TFs) and, hence, deregulating expression nearby genes. These aspects understudied due sheer number TF binding motifs, making it challenging identify that yield phenotypic changes altered gene expression. Results We developed a data-driven computational protocol prioritize high-potential informed from former knowledge experimental validation. evaluated by investigating CREs Janus kinase (JAK) – Signal Transducer Activator Transcription (-STAT) signaling pathway, which is activated plethora cytokines crucial controlling immune responses has implicated diseases like cancer, autoimmune disorders, viral infections. The involves scanning entire human genome (hg38) pinpoint DNA sequences deviate only canonical sites (TTCnnnGAA) STAT TFs. narrowed down an initial pool 3,301,512 across 17,039,967 nearly complete six potential gain-of-function regions likely influence regulation within JAK-STAT pathway. This selection was guided publicly available open chromatin data further refined filtering proximity response genes conservation between mouse genomes. Conclusion Our findings highlight value combining genomic, epigenomic, cross-species effectively narrow millions smaller with high induce interferon finally reviewed manually, laying groundwork more focused efficient exploration regulatory setting.

Language: Английский

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Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102467 - 102467

Published: March 1, 2025

Language: Английский

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Mechanical factors influence β-catenin localization and barrier properties

Integrative Biology, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 1, 2024

Abstract Mechanical forces are of major importance in regulating vascular homeostasis by influencing endothelial cell behavior and functions. Adherens junctions critical sites for mechanotransduction cells. β-catenin, a component adherens the canonical Wnt signaling pathway, plays role mechanoactivation. Evidence suggests that β-catenin is involved flow sensing responds to tensional forces, impacting junction dynamics. The mechanoregulation context-dependent, influenced type duration mechanical loads. In cells, β-catenin’s nuclear translocation shear stress strain, affecting permeability. study investigates how stress, surface topography impact dynamics, regulate localization, influence barrier properties. Insight box loads potent regulators functions through not completely elucidated mechanisms. Surface topography, wall cyclic deformation contribute overlapping stimuli which monolayer respond adapt maintain use custom developed chamber bioreactor allows quantifying response mature human well-defined gradients strain. Here, substrate stretch analyzed linked control

Language: Английский

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Transcriptomic profiling analysis of the effect of palmitic acid on 3D spheroids of β-like cells derived from induced pluripotent stem cells

Gene, Journal Year: 2024, Volume and Issue: 917, P. 148441 - 148441

Published: April 10, 2024

Language: Английский

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Assessing next-generation sequencing-based computational methods for predicting transcriptional regulators with query gene sets

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(5)

Published: July 25, 2024

Abstract This article provides an in-depth review of computational methods for predicting transcriptional regulators (TRs) with query gene sets. Identification TRs is utmost importance in many biological applications, including but not limited to elucidating development mechanisms, identifying key disease genes, and therapeutic targets. Various based on next-generation sequencing (NGS) data have been developed the past decade, yet no systematic evaluation NGS-based has offered. We classified these into two categories shared characteristics, namely library-based region-based methods. further conducted benchmark studies evaluate accuracy, sensitivity, coverage, usability molecular experimental datasets. Results show that BART, ChIP-Atlas, Lisa relatively better performance. Besides, we point out limitations explore potential directions improvement.

Language: Английский

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Computational Reconstruction of the Transcription Factor Regulatory Network Induced by Auxin in Arabidopsis thaliana L.

Plants, Journal Year: 2024, Volume and Issue: 13(14), P. 1905 - 1905

Published: July 10, 2024

In plant hormone signaling, transcription factor regulatory networks (TFRNs), which link the master factors to biological processes under their control, remain insufficiently characterized despite crucial function. Here, we identify a TFRN involved in response key auxin and define its impact on auxin-driven processes. To reconstruct TFRN, developed three-step procedure, is based integrated analysis of differentially expressed gene lists representative collection binding profiles. Its implementation available as part CisCross web server. With new method, distinguished two subnetworks. The first operates before treatment switched off upon application, second by hormone. Moreover, functioning auxin-regulated control chlorophyll lignin biosynthesis, abscisic acid ribosome biogenesis.

Language: Английский

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Leveraging independent component analysis to unravel transcriptional regulatory networks: A critical review and future directions

Biotechnology Advances, Journal Year: 2024, Volume and Issue: unknown, P. 108479 - 108479

Published: Nov. 1, 2024

Language: Английский

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