Biology subjects

Shay, T.

Publications and source records attributed to Shay, T..

5 recordsLinked to original sources

bioRxiv2026

Alternative splicing use ratio is not conserved between human and mouse immune cells

Most human genes have mouse orthologs. However, orthology at the level of exons and alternative splicing events is not well defined, and the use of alternative splicing events in immune cell types has not been compared between human and mouse. We mapped exons and alternative splicing events between human and mouse. Based on this mapping, the use ratio of orthologous alternative splicing events was compared between human and mouse immune cell types and fibroblasts. Out of the 1,823 human-mouse orthologous alternative splicing events that are expressed in the five tested immune cell types, most (62-67%) showed a significant difference in use ratio between human and mouse, and less than third (21-25%) retained the same ratio. Our results reveal both conserved and divergent alternative splicing usage ratio, and highlight the dynamic evolution of alternative splicing regulation across human and mouse immune cell types. By integrating exon orthology with observed splicing patterns, our analysis provides a functional framework for studying mammalian splicing ratio evolution beyond static transcript annotations.

immunology↗

bioRxiv2023

A telencephalon cell type atlas for goldfish reveals diversity in the evolution of spatial structure and cell types

Teleost fish form the largest group of vertebrates, making them critically important for the study on the mechanisms of brain evolution. In fact, teleosts show a tremendous variety of adaptive behaviors similar to birds and mammals, however, the neural basis mediating these behaviors remains elusive. We performed a systematic comparative survey of the goldfish telencephalon; the seat of plastic behavior, learning and memory in vertebrates. We delineated and mapped goldfish telencephalon cell types using single-cell RNA-seq and spatial transcriptomics, resulting in de novo molecular neuroanatomy parcellation. Glial cells were highly conserved across 450 million years of evolution separating mouse and goldfish, while neurons showed diversity and modularity in gene expression. Specifically, somatostatin (SST) interneurons, famously interspersed in the mammalian isocortex for local inhibitory input, were curiously aggregated in a single goldfish telencephalon nucleus, but molecularly conserved. Cerebral nuclei including the striatum, a hub for motivated behavior in amniotes, had molecularly and spatially conserved goldfish homologues. We further suggest different elements of a hippocampal formation across the goldfish pallium. Together, our atlas provides new insights to organization and evolution of vertebrate forebrains and may serve as a resource for the functional study underlying cognition in teleost fish. TeaserDetailed mapping of goldfish forebrain cells unwraps how 450 million years of evolution may have impacted brain function

neuroscience↗

bioRxiv2020

DoChaP: The Domain Change Presenter

Alternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon-domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain-exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon-domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.

bioinformatics↗

bioRxiv2018

Conservation and divergence in modules of the transcriptional programs of the human and mouse immune systems

Studies in mouse have shed important light on human hematopoietic differentiation and disease. However, substantial differences between the two species often limit the translation of findings from mouse to human.\n\nHere, we compare previously defined modules of co-expressed genes in human and mouse immune cells based on compendia of genome-wide profiles. We show that the overall modular organization of the transcriptional program is conserved. We highlight modules of co-expressed genes in one species that dissolve or split in the other species. Many of the associated regulatory mechanisms - as reflected by computationally inferred trans regulators, or enriched cis-regulatory elements - are conserved between the species. Nevertheless, the degree of conservation in regulatory mechanism is lower than that of expression, suggesting that distinct regulation may underlie some of the conserved transcriptional responses.

bioinformatics↗

bioRxiv2017

Salient Experiences are Represented by Unique Transcriptional Signatures in the Brain

Inducible transcription is essential for consolidation of salient experiences into long-term memory. However, the question of whether inducible transcription relays information representing the identity of the experience being encoded, has not been explored. To this end, we have analyzed transcription across multiple brain regions, induced by a variety of rewarding and aversive experiences. Our results define robust transcriptional signatures uniquely characterizing individual salient experiences. A subset of these induced transcriptional markers suffice for near-perfect decoding of the identity of recent experiences at the level of individual mice. Furthermore, experiences with shared attributes display commonalities in their transcriptional representation, exemplified in the representation of valence, habituation and reinforcement. Taken together, our results demonstrate the existence of a neural transcriptional code that represents the encoding of experiences in the mouse brain. This code is comprised of distinct transcriptional signatures that correlate to the affective attributes of the experiences that are being encoded.

neuroscience↗