Carlos F Buen Abad Najar

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PhD candidate, Computational Biology. UC Berkeley. Lareau lab and Yosef lab

cfbuenabadn [at] berkeley [dot] edu

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I am a postdoctoral scholar at the University of Chicago Department of Medicine since August 2021. I work with with Dr Yang I. Li and Dr Matthew Stephens.

I recieved my BSc in Biology from Universidad Nacional Autonoma de Mexico in 2015. I earned a PhD in Computational Biology at UC Berkeley in 2021, with the advise of Dr Liana Lareau and Dr Nir Yosef. My PhD research focused in analysing alternative splicing in single cell RNA-sequencing (scRNA-seq) data, and in the regulation of splicing of ultraconserved poison exons.

Alternative splicing in single cells

Observations of alternative splicing with scRNA-seq led to an unexpected observation: in a homogeneous population of single cells, most cells consistently show either one isoform or another of the same gene, but they rarely produce both. In other words, the apparent distribution of the Percent Spliced-In (Ψ) of isoforms is bimodal and mostly binary. In recent work, I showed that the distortion of the observed Ψ by low capture efficiency and amplification biases are the main source of this apparent bimodality in full-transcript scRNA-seq data. The challenge for Computational Biologists ahead is to account for these biases in the analysis of informative alternative splicing at the single cell level.

In light of these observations, we developed Psix: a probabilistic approach to identify cell-state associated exons in scRNA-seq. Chek out the pre-print here.

Regulation of poison exon splicing

Ultraconserved poison exons are a fascinating yet largely unknown mechanism of post-transcriptional regulation in the Serine/Argenine-Rich (SR) family of splicing factors. I am currently working on analysing the binding patterns of RNA Binding Proteins (RBPs) in these exons in order to reveal potential regulatory mechanisms.