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Konrad @konradjk.bsky.social · 12h

gs://ukb-diverse-pops-public/misc/pairwise/pairwise_correlations_regressed.txt.bgz - it’s coded in the way that our pan-UKB phenotypes were so not sure if it’s super easy to use but that’s pairwise r_p for ~14k phenos

Konrad @konradjk.bsky.social · 20d

Special thanks to all co-authors that got this here including @masakanai.bsky.social @rahulg603.bsky.social @dalygene.bsky.social @egatkinson.bsky.social and of course @genetisaur.bsky.social for driving this through 5 years of work (after the first GWASes were done!)

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Konrad @konradjk.bsky.social · 20d

Tons of lessons learned around carefully controlling population stratification, using heritability as a QC metric, and probably most importantly, quantifying novelty in a mega-phenotype analysis. Some really cool analyses to find interesting biology e.g. allelic series and ancestry-enriched variants

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Konrad @konradjk.bsky.social · 20d

A project many years in the process, we’re pleased to present our work on multi-ancestry meta-analysis across a boatload of traits in the UK Biobank: www.nature.com/articles/s41...

Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects - Nature Genetics

Genome-wide analyses for 7,266 traits leveraging data from several genetic ancestry groups in UK Biobank identify new associations and enhance resources for interpreting risk variants across diverse p...

www.nature.com

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Konrad @konradjk.bsky.social · Nov 8

We’ve put up summary statistics for over 3,000 traits in the All of Us resource, and a shiny new browser alongside it! Explore your favorite gene or phenotype here: allbyall.researchallofus.org #ASHG24

All by All

The All by All browser maps known and novel associations between genotypes and phenotypes using data contributed by All of Us Research Program participants as of July 1, 2022. All by All encompasses a...

allbyall.researchallofus.org

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Konrad @konradjk.bsky.social · Nov 8

Starter pack of people who create starter packs?

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Konrad @konradjk.bsky.social · Nov 7

You mean “ReNally???”?

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Konrad @konradjk.bsky.social · Sep 21

Heh, it was on our list but somehow never made it into the pre-submission checklist. Will do!

Konrad @konradjk.bsky.social · Sep 20

Interesting question. We do have a “gnomAD-new” analysis in there but haven’t broken down by ancestry - i fear a lot is going to be driven by “not yet observed” (which is the same across all ancestries)

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Konrad @konradjk.bsky.social · Sep 20

It gets a bit more complicated though - these scores have a mix of impacts of variant-to-gene, as well as prioritizing which genes, when disrupted, lead to phenotypes. Perhaps a new method that combines both these insights optimally will outperform them all!

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Konrad @konradjk.bsky.social · Sep 20

We found that population-focused methods do best for identifying highly impactful variants (de novo’s in individuals with developmental disorders for instance), while the deep learning methods are better at prioritizing inherited variation in biobanks

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Konrad @konradjk.bsky.social · Sep 20

We have a new preprint that we’d love feedback on! We benchmarked a bunch of variant scoring methods to figure out what they were actually doing, and how they performed across selection regimes: www.biorxiv.org/content/10.1...

Variant scoring performance across selection regimes depends on variant-to-gene and gene-to-disease components

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

www.biorxiv.org

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Konrad @konradjk.bsky.social · Sep 20

Welcome new followers (and thanks @michelnivard.bsky.social)! I’m loving the critical mass, and to celebrate, I’ll post some exciting new content (my first time posting here and not on the the other site)

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Reposted by Konrad

Kaitlin Samocha @ksamocha.bsky.social · Apr 19

Recently out on #bioRxiv: our updated approach to identify regional variability in missense mutation intolerance (“constraint”) in protein-coding genes using the gnomAD database.

www.biorxiv.org/content/10.1...

1/10

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Konrad @konradjk.bsky.social · Jan 31

As genomic analyses scale to millions of exomes/genomes, we need a scalable infrastructure to process/QC/handle these data while retaining all the metrics needed for downstream analysis. A new preprint from the Hail team proposes a way to do this! Comments welcome: www.biorxiv.org/content/10.1...

The Scalable Variant Call Representation: Enabling Genetic Analysis Beyond One Million Genomes

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

www.biorxiv.org

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Konrad @konradjk.bsky.social · Dec 7

Paella is good. With LOEUF I assumed the culmination would be an omelette but CHARR is better in a paella, so maybe it’s a multi-course meal

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Konrad @konradjk.bsky.social · Dec 7

Extended data figure 2b has exclusive exon-only. I think we internally made some with intermediate overlaps and it was an intermediate result as you’d expect

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Konrad @konradjk.bsky.social · Dec 6

And thanks to Ryan Dhindsa and Slavé Petrovski for the excellent writeup and context around our work. Excited for the times ahead! www.nature.com/articles/d41...

An expanded genomic database for identifying disease-related variants

An expanded version of a human-genome database called gnomAD, containing 76,156 whole-genome sequences, has enabled investigation of how variants in non-protein-coding regions of the genome affect hea...

www.nature.com

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Konrad @konradjk.bsky.social · Dec 6

This is all thanks to an amazing production team, browser team, and steering committee @gnomad-project.bsky.social, the 76,156 individuals that provided their genomes, and support from Broad Genomics and Hail

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Konrad @konradjk.bsky.social · Dec 6

Interestingly, these scores also provide additional insight into genes regulated by these regions, even those underpowered by previous constraint metrics:

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Konrad @konradjk.bsky.social · Dec 6

Gnocchi extends our constraint metrics to the non-coding genome, highlighting for instance, disease-associated non-coding CNVs

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Konrad @konradjk.bsky.social · Dec 6

We built a new metric we called gnocchi (genomic non-coding constraint of haploinsufficient variation), building on methods that find depletions of variation (natural selection), which we show can prioritize functional variation

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Konrad @konradjk.bsky.social · Dec 6

Thrilled to have our work on gnomAD out in print at Nature today. With 76K genomes, we can look beyond the coding genome and into the non-coding genome to find regions important for human disease idp.nature.com/authorize?re...

A genomic mutational constraint map using variation in 76,156 human genomes - Nature

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulator...

idp.nature.com

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Konrad @konradjk.bsky.social · Nov 28

Thanks to Wenhan Lu for driving this effort, Hail (hail.is) for building the scalable infrastructure that enabled this, and @gnomAD-project.bsky.social for the data and support

Hail | Index

hail.is

Konrad @konradjk.bsky.social · Nov 28

CHARR operates only on homozygous alternate sites and scales very well (“cost per 1M samples” might be my new favorite metric):

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