Sudarshan Pinglay

How much of the human genome is essential? Two pieces out today from our lab: 1) a method to map essential genomic intervals at gigabase scale, and 2) an argument that it's time to consider synthesizing a minimal human genome. biorxiv.org/content/10.648… nature.com/articles/d4158…

@anshulkundaje Thanks Anshul! Cannot agree more!

Academic labs continue to lead on next generation tech dev for powering AI models for biology. The next big leap in models of gene regulation will be when they truly master the long range functional architecture of the genome. 1/

@danofer Available in the supplemental data files! And see Fig. 3 and 4

@sudpinglay Is there a nice BED or similar file (to filter UCSC/genome tracts)? How well does it align with TAD boundaries?

How much of the human genome is essential? Two pieces out today from our lab: 1) a method to map essential genomic intervals at gigabase scale, and 2) an argument that it's time to consider synthesizing a minimal human genome. biorxiv.org/content/10.648… nature.com/articles/d4158…

@drrichjlaw We can't do this very well at the moment but that's exactly why it's worth doing. Applying Shred-seq (see accompanying preprint) to differentiation and reprogramming systems is one way to move beyond descriptive annotations to an empirical determination of what is essential

@sudpinglay For 2), how much can it take into account how poorly annotated & [publically] understood the regulatory (non-coding) genome is in maintaining cell state programming & even partial cellular programming?

@ProfTomEllis thanks Tom! Totally agree with you

@sudpinglay More work like ShredSeq and Genome Scramble, combined with RNAseq is desperately needed to train these models to handle what happens when genes and promoters are put in very different genomic contexts, like minimal chromosomes.

huge thank you to all the co-authors and in particular, @JonasKoeppel @JShendure for helping leading this effort! also big thanks to @BrotmanBaty @NIH_CommonFund @genome_gov @biohub @DARPA for funding!

Looking forward to engaging further with the community on these ideas. If you're excited about working in these areas, we are hiring! pinglay-lab.com

@rovingscientist Thanks Sumantra! There any many possible minimal genomes depending on cellular context. Simplest form: what is the minimal genetic information required to support the life and division of a single mammalian cell line? Adding in other functionalties would give us different answers

@sudpinglay Congrats! Great work! I have wondered about this minimal human genome since Craig Venter made the “minimal genome containing cell”.. i guess the philosophical question is what are the fucntions a cell need to perform to consider it a functinonal unit?

1/n What fraction of the human genome is essential for cellular viability? Excited to share our preprint that explores this question by combining an unusual CRISPR system, phage promoters, and thousands of deletion launchpads. @sudpinglay @JShendure biorxiv.org/content/10.648…

Characterizing AI-designed proteins requires quantitative biochemistry at massive scale. Enter Amplicon/Protein Bead Display (APB-Display), a fully in vitro platform that quantifies Kd's for >100,000 variants in <3 days (preprint link below!) @Stanford_ChEMH @czbiohub (1/n)

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.