Biology subjects

Yarden Katz

Publications and source records attributed to Yarden Katz.

4 recordsLinked to original sources

bioRxiv2016

Probabilistic adaptation in changing microbial environments

Microbes growing in animal host environments face fluctuations that have elements of both randomness and predictability. In the mammalian gut, fluctuations in nutrient levels and other physiological parameters are structured by the animal hosts behavior, diet, health and microbiota composition. Microbial cells that are able to anticipate these fluctuations by exploiting this structure would likely gain a fitness advantage, by adapting their internal state in advance. We propose that the problem of adaptive growth in these structured changing environments can be viewed as probabilistic inference. We analyze environments that are \"meta-changing\": where there are changes in the way the environment fluctuates, governed by a mechanism unobservable to cells. We develop a dynamic Bayesian model of these environments and show that a real-time inference algorithm (particle filtering) for this model can be used as a microbial growth strategy implementable in molecular circuits. The growth strategy suggested by our model outperforms heuristic strategies, and points to a class of algorithms that could support real-time probabilistic inference in natural or synthetic cellular circuits.

Systems Biology↗

bioRxiv2014

Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state

SummaryThe conserved Musashi (Msi) family of RNA binding proteins are expressed in stem/progenitor and cancer cells, but mostly absent from differentiated cells, consistent with a role in cell state regulation. We found that Msi genes are rarely mutated but frequently overexpressed in human cancers, and associated with an epithelial-luminal cell state. Using ribosome footprint profiling and RNA-seq analysis of genetic mouse models in neuronal and mammary cell types, we found that Msis regulate translation of genes implicated in epithelial cell biology and epithelial-to-mesenchymal transition (EMT) and promote an epithelial splicing pattern. Overexpression of Msi proteins inhibited translation of genes required for EMT, including Jagged1, and repressed EMT in cell culture and in mammary gland in vivo, while knockdown in epithelial cancer cells led to loss of epithelial identity. Our results show that mammalian Msi proteins contribute to an epithelial gene expression program and promote an epithelial-luminal state in both neural and breast cell types.\n\nHighlightsO_LIMsi proteins bind UAG motifs in vitro and in 3 UTRs of mRNAs\nC_LIO_LIMsi proteins are markers of epithelial state in brain and breast tumors, and cell lines\nC_LIO_LIThe Notch regulator Jag1 mRNA is bound and translationally repressed by Msi\nC_LIO_LIMsi overexpression represses EMT in the mammary gland in vivo\nC_LI

Genomics↗

bioRxiv2014

Rapid transcriptional response to physiological neuronal activity in vivo revealed by transcriptome sequencing

Neuronal activity serves as a gateway between external stimulus from environment and the brain, often inducing gene expression changes. Alternative splicing (AS) is a widespread mechanism of increasing the number of transcripts produced from a single gene and has been shown to alter properties of neuronal genes, such as ion channels (Xie and Black 2001) and neurotransmitter receptors (Mu et al. 2003). Patterns of neural tissue-specific AS have been identified, often regulated by neuron-specific splicing factors that are essential for survival (Jensen et al. 2000; Li et al. 2007), demonstrating the importance of AS in neurons. In vitro studies of neuronal activity found AS changes in response to neuronal activity in addition to transcriptional ones, raising the question of whether such changes are recapitulated in vivo on behaviorally relevant timescales. We developed a paradigm for studying physiological neuronal activity through controlled stimulation of the olfactory bulb, and performed RNA-Seq transcriptome analysis of olfactory bulbs from odor-deprived and stimulated mice. We found that physiological stimulation induces large, rapid and reproducible changes in transcription in vivo, and that the activation of a core set of activity-regulated factors is recapitulated in an in vitro model of neuronal stimulation. However, physiological activity did not induce global changes in post-transcriptional mRNA processing, such as AS or alternative cleavage and polyadenylation. In contrast, analysis of RNA-Seq from in vitro stimulation models showed rapid activity-dependent changes in both transcription and mRNA processing. Our results provide the first genome-wide look at neuronal activity-dependent mRNA processing and suggest that rapid changes in AS might not be the dominant form of transcriptome alterations that take place during olfactory rodent behavior.

Neuroscience↗

bioRxiv2014

Sashimi plots: Quantitative visualization of alternative isoform expression from RNA-seq data

To the Editor: To the Editor: Software documentation and... References Analysis of RNA sequencing (RNA-Seq) data revealed that the vast majority of human genes express multiple mRNA isoforms, produced by alternative pre-mRNA splicing and other mechanisms, and that most alternative isoforms vary in expression between human tissues (Pan et al., 2008; Wang et al., 2008). As RNA-Seq datasets grow in size, it remains challenging to visualize isoform expression across multiple samples. We present Sashimi plots, a quantitative multi-sample visualization of RNA-Seq reads aligned to gene annotations, which enables quantitative comparison of isoform usage across samples or experimental conditions. Given an input annotation and spliced alignments of reads from a sample, a region of interest is visualized in a Sashimi plot as follows: (i) alignments in ...

Bioinformatics↗