GUIDE deconstructs genetic architectures using association studies biorxiv.org/cgi/content/sh… #biorxiv_genetic

Could not be more delighted to present our work investigating how over 220,000 complex and molecular trait-associated genetic variants affect transcriptional regulation using massively parallel reporter assays!
biorxiv.org/content/10.110…
See below for a 🧵. 1/n

After 20 years and 42 days, Illumina's patent covering DNA microarray normalization, clustering, and genotyping, together known as Illumina GenCall, filed on March 24th 2004, has expired patentcenter.uspto.gov/applications/1… 1/8

🚨🔊Interested in structural variants? Genome sequencing? Pediatric cancers? Germline variants+cancer risk? Rare variants+rare diseases?

If so (or even if not!), I'm delighted to share the first paper from my postdoc Eli Van Allen Dana-Farber:

biorxiv.org/content/10.110…

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Would you believe me if I told you that a single variant in a non-coding RNA explains ~0.5% of all undiagnosed individuals with neurodevelopmental disorders (NDD) in Genomics England ???

I didn’t initially either, but here is the story of RNU4-2 🧵1/9

Blended Genome Exome (BGE) as a Cost Efficient Alternative to Deep Whole Genomes or Arrays biorxiv.org/content/10.110…

Thrilled to see our work on chemically and topologically engineered mRNA online! Using a chemo-enzymatic approach, we introduced multiple end-modified polyA tails on a single mRNA to boost its stability and translatability overtime. nature.com/articles/s4158…

Infertility affects 1 in 6 couples across the globe, but its cause remains unknown in over 30% of cases 😔 In our latest work with Cecilia Lindgren, we discover rare and common genetic variants associated with infertility in 🇬🇧🇩🇰🇪🇪🇫🇮🇮🇸 medrxiv.org/content/10.110… Thread ⬇️

I remember reading this in 2022 as a preprint. Glad to see this work by Satu Strausz, Michal Tal, PhD, Hanna M Ollila and team in published form. This is a nice example of a low-hanging fruit that didn't get picked early because no one studied the phenotype. Performing a GWAS of Lyme

4 years ago, we ran 16,554 GWASes for 7,271 traits across 6 ancestry groups and released the data to the public along with meta-analysis. After many careful dives through the results, we are happy to present these analyses on behalf of the Pan-UKB Project: medrxiv.org/content/10.110…

I'm excited to share this new preperint with Matt Pennell and Doc Edge about the unifying mapping approaches within and between species biorxiv.org/content/10.110…

1/ We’re excited to share our new preprint “Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions” available on medRxiv! medrxiv.org/content/10.110…

Congrats Dan King on leading the Hail team and the transformative science it has enabled! Wishing you the best moving forward.

This is a fantastic opportunity to lead scalable open-source compute as the big data/omics revolution charges forth! #compbio #genomics #opensource

Oh cool nice to know the developers thought making an originally undocumented change that could dramatically alter downstream interpretation was obvious for them

New manuscript about BCFtools/liftover, a tool that converts genetic variants between reference genome assemblies with better support for indels and multi-allelic variants: academic.oup.com/bioinformatics… 1/8

Structural variants (SV) impact more nucleotides per human genome than other forms of genetic variation.

To better understand SV impact, we developed a method to 'shuffle' mammalian genomes and characterize them with single-cell resolution in a pool.

biorxiv.org/content/10.110…

It took 8 years, but Hail finally wrote a paper!

The SVCR is essentially a multi-sample generalization of the GVCF. We realize it in both VCF and Hail MT formats.

It generated & analyzed many callsets; including 240k WGS and 955k WES.

biorxiv.org/content/10.110…

Our team - Alex, Maxim Artyomov and Mark Daly has developed the algorithm for genetic association studies without individual-level data sharing and a resource with 39,472 exomes to be used as a pool of controls. It is now available at Nature Genetics! nature.com/articles/s4158…

New paper by Jiacheng Miao! We often want to study traits that are difficult/expensive to measure. It's becoming popular to use machine learning to predict these phenotypes in large cohorts, then perform GWAS on imputed outcomes. It may be a bad idea!
medrxiv.org/content/10.110…

Our paper on the development of a human genetics-guided score to prioritize drug target genes is online now in Nature Genetics Nature Genetics

Paper: nature.com/articles/s4158…

Share link: rdcu.be/du2ZR

Press release: mountsinai.org/about/newsroom…

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