Bill Mowrey
@billbio.bsky.social
Principal Scientist at Alexion, AstraZeneca Rare Disease (views are my own)
Reposted by Bill Mowrey
The effects of genetic variants primarily occur in differentiated cells meaning we need to access these cell types to measure variant effects for most disease genes. We developed saturation genome editing in stem cells (iPSC-SGE) to enable phenotyping in diverse genetic and cell contexts at scale!
Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts
Multiplexed assays of variant effect (MAVEs) systematically measure variant function but have been limited to cancer cell lines rather than disease-relevant cell types. We developed saturation genome ...
www.medrxiv.org
November 22, 2025 at 1:49 AM
The effects of genetic variants primarily occur in differentiated cells meaning we need to access these cell types to measure variant effects for most disease genes. We developed saturation genome editing in stem cells (iPSC-SGE) to enable phenotyping in diverse genetic and cell contexts at scale!
Reposted by Bill Mowrey
I wrote a little bit about the "missing heritability" question and several recent studies that have brought it to a close. A short 🧵
The missing heritability question is now (mostly) answered
Not with a bang but with a whimper
theinfinitesimal.substack.com
November 21, 2025 at 10:34 PM
I wrote a little bit about the "missing heritability" question and several recent studies that have brought it to a close. A short 🧵
Reposted by Bill Mowrey
The amazing @shawnfayer.bsky.social has developed a saturation genome editing method in iPSCs enabling MAVEs in differentiated cell types and diploid contexts. Please check it out!
And, for some lucky department, Shawn is on the faculty job market!
And, for some lucky department, Shawn is on the faculty job market!
The effects of genetic variants primarily occur in differentiated cells meaning we need to access these cell types to measure variant effects for most disease genes. We developed saturation genome editing in stem cells (iPSC-SGE) to enable phenotyping in diverse genetic and cell contexts at scale!
Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts
Multiplexed assays of variant effect (MAVEs) systematically measure variant function but have been limited to cancer cell lines rather than disease-relevant cell types. We developed saturation genome ...
www.medrxiv.org
November 23, 2025 at 11:44 PM
The amazing @shawnfayer.bsky.social has developed a saturation genome editing method in iPSCs enabling MAVEs in differentiated cell types and diploid contexts. Please check it out!
And, for some lucky department, Shawn is on the faculty job market!
And, for some lucky department, Shawn is on the faculty job market!
Reposted by Bill Mowrey
🚨Big News!🚨
Our keynote lineup for the ASHG Genetic Diagnosis & Rare Disease Virtual Symposium is here!
Dec 2: @ahrensnicklas.bsky.social & @kiranmusunuru.bsky.social
Dec. 3: Helene Cederroth & Eric Klee
You won't want to miss their insights shaping rare disease genetics: bit.ly/3WVd6l2 #ASHG
Our keynote lineup for the ASHG Genetic Diagnosis & Rare Disease Virtual Symposium is here!
Dec 2: @ahrensnicklas.bsky.social & @kiranmusunuru.bsky.social
Dec. 3: Helene Cederroth & Eric Klee
You won't want to miss their insights shaping rare disease genetics: bit.ly/3WVd6l2 #ASHG
November 21, 2025 at 4:22 PM
🚨Big News!🚨
Our keynote lineup for the ASHG Genetic Diagnosis & Rare Disease Virtual Symposium is here!
Dec 2: @ahrensnicklas.bsky.social & @kiranmusunuru.bsky.social
Dec. 3: Helene Cederroth & Eric Klee
You won't want to miss their insights shaping rare disease genetics: bit.ly/3WVd6l2 #ASHG
Our keynote lineup for the ASHG Genetic Diagnosis & Rare Disease Virtual Symposium is here!
Dec 2: @ahrensnicklas.bsky.social & @kiranmusunuru.bsky.social
Dec. 3: Helene Cederroth & Eric Klee
You won't want to miss their insights shaping rare disease genetics: bit.ly/3WVd6l2 #ASHG
Reposted by Bill Mowrey
First time on Bsky and first big announcement!
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
Estimation and mapping of the missing heritability of human phenotypes - Nature
WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 co...
www.nature.com
November 12, 2025 at 5:57 PM
First time on Bsky and first big announcement!
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
Reposted by Bill Mowrey
How do GWAS and rare variant burden tests rank gene signals?
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
Specificity, length and luck drive gene rankings in association studies - Nature
Genetic association tests prioritize candidate genes based on different criteria.
www.nature.com
November 7, 2025 at 12:05 AM
How do GWAS and rare variant burden tests rank gene signals?
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
Reposted by Bill Mowrey
📍Pinned Post: Welcome to the papers with code feed!
bsky.app/profile/did:...
Papers from PubMed, bioRxiv, Bature, PLoS, etc, with links to GitHub will be included here. Anyone can post to this feed.
See also: blog.stephenturner.us
bsky.app/profile/did:...
Papers from PubMed, bioRxiv, Bature, PLoS, etc, with links to GitHub will be included here. Anyone can post to this feed.
See also: blog.stephenturner.us
December 5, 2024 at 10:05 AM
📍Pinned Post: Welcome to the papers with code feed!
bsky.app/profile/did:...
Papers from PubMed, bioRxiv, Bature, PLoS, etc, with links to GitHub will be included here. Anyone can post to this feed.
See also: blog.stephenturner.us
bsky.app/profile/did:...
Papers from PubMed, bioRxiv, Bature, PLoS, etc, with links to GitHub will be included here. Anyone can post to this feed.
See also: blog.stephenturner.us
Reposted by Bill Mowrey
Noori, Banday, Voskoboinik et al use recently developed in vitro technology to define the function of a previously uncharacterized STX11 mutation L135P in a patient w/ atypical familial hemophagocytic lymphohistiocytosis. rupress.org/jhi/article/...
🎥 See a video summary: youtu.be/cYSBIU0lh6U
🎥 See a video summary: youtu.be/cYSBIU0lh6U
Partial STX11 deficiency due to a hypomorphic variant—self-limiting inflammatory disease preceding HLH onset | Journal of Human Immunity | Rockefeller University Press
Recently developed in vitro technology was used to define the function of a previously uncharacterized STX11 mutation L135P present in a patient with atypi
rupress.org
October 21, 2025 at 5:59 PM
Noori, Banday, Voskoboinik et al use recently developed in vitro technology to define the function of a previously uncharacterized STX11 mutation L135P in a patient w/ atypical familial hemophagocytic lymphohistiocytosis. rupress.org/jhi/article/...
🎥 See a video summary: youtu.be/cYSBIU0lh6U
🎥 See a video summary: youtu.be/cYSBIU0lh6U
Reposted by Bill Mowrey
Now online @nature.com!
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Designing allosteric modulators to change GPCR G protein subtype selectivity - Nature
Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor su...
www.nature.com
October 27, 2025 at 8:50 PM
Now online @nature.com!
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Reposted by Bill Mowrey
“Cellular Olympics” our catalog of freeky ultra fast cellular superhero’s is freely available “Ann Rev of microbiology”
www.annualreviews.org/content/jour...
This is a compilation of world’s fastest single cell organisms - enjoy this buffet of rare delightful protists with mind bending speeds. 🧪
www.annualreviews.org/content/jour...
This is a compilation of world’s fastest single cell organisms - enjoy this buffet of rare delightful protists with mind bending speeds. 🧪
October 24, 2025 at 10:57 AM
“Cellular Olympics” our catalog of freeky ultra fast cellular superhero’s is freely available “Ann Rev of microbiology”
www.annualreviews.org/content/jour...
This is a compilation of world’s fastest single cell organisms - enjoy this buffet of rare delightful protists with mind bending speeds. 🧪
www.annualreviews.org/content/jour...
This is a compilation of world’s fastest single cell organisms - enjoy this buffet of rare delightful protists with mind bending speeds. 🧪
Reposted by Bill Mowrey
Cracking the code of the non-coding genome via allele-specific genomics?
Can we link non-coding elements—like lncRNAs and enhancers—to their protein-coding target genes, and in doing so, connect overlapping non-coding disease variants to their protein-coding counterparts?
Can we link non-coding elements—like lncRNAs and enhancers—to their protein-coding target genes, and in doing so, connect overlapping non-coding disease variants to their protein-coding counterparts?
October 24, 2025 at 2:44 AM
Cracking the code of the non-coding genome via allele-specific genomics?
Can we link non-coding elements—like lncRNAs and enhancers—to their protein-coding target genes, and in doing so, connect overlapping non-coding disease variants to their protein-coding counterparts?
Can we link non-coding elements—like lncRNAs and enhancers—to their protein-coding target genes, and in doing so, connect overlapping non-coding disease variants to their protein-coding counterparts?
Reposted by Bill Mowrey
Why do complex traits differ in their genetic architecture?
In our new PLOS Biology paper, we will try to convince you that two simple scaling laws drive differences in the number, effect sizes and frequencies of causal variants affecting complex traits.
Thread:
journals.plos.org/plosbiology/...
In our new PLOS Biology paper, we will try to convince you that two simple scaling laws drive differences in the number, effect sizes and frequencies of causal variants affecting complex traits.
Thread:
journals.plos.org/plosbiology/...
Simple scaling laws control the genetic architectures of human complex traits
Genome-wide association studies have revealed that the genetic architectures of complex traits vary widely. This study shows that differences in architectures of highly polygenic traits arise mainly f...
journals.plos.org
October 24, 2025 at 1:51 AM
Why do complex traits differ in their genetic architecture?
In our new PLOS Biology paper, we will try to convince you that two simple scaling laws drive differences in the number, effect sizes and frequencies of causal variants affecting complex traits.
Thread:
journals.plos.org/plosbiology/...
In our new PLOS Biology paper, we will try to convince you that two simple scaling laws drive differences in the number, effect sizes and frequencies of causal variants affecting complex traits.
Thread:
journals.plos.org/plosbiology/...
Lasting piece of what?
October 23, 2025 at 12:51 PM
Lasting piece of what?
Reposted by Bill Mowrey
Analyses of U.K. Biobank and clinical cohorts show that rare genetic diseases can be misdiagnosed as common diseases, which may have implications for clinical trials as well as for diagnosis and treatment. Full study results: nej.md/3Jk1MvD
#MedSky #Genetics
#MedSky #Genetics
October 22, 2025 at 9:10 PM
Analyses of U.K. Biobank and clinical cohorts show that rare genetic diseases can be misdiagnosed as common diseases, which may have implications for clinical trials as well as for diagnosis and treatment. Full study results: nej.md/3Jk1MvD
#MedSky #Genetics
#MedSky #Genetics
Reposted by Bill Mowrey
@biorxivpreprint.bsky.social Precision targeting of autoreactive B cells in systemic lupus erythematosus using anti-9G4 idiotope synthetic immune receptor T cells
www.biorxiv.org/content/10.1...
Great work @maxkonigmd.bsky.social
www.biorxiv.org/content/10.1...
Great work @maxkonigmd.bsky.social
October 21, 2025 at 1:33 AM
@biorxivpreprint.bsky.social Precision targeting of autoreactive B cells in systemic lupus erythematosus using anti-9G4 idiotope synthetic immune receptor T cells
www.biorxiv.org/content/10.1...
Great work @maxkonigmd.bsky.social
www.biorxiv.org/content/10.1...
Great work @maxkonigmd.bsky.social
Reposted by Bill Mowrey
It was fun writing this essay, about bottom-up neuroscience and how we might simulate entire brains, using data collected via new technologies (expansion microscopy, optogenetics, whole brain voltage imaging, and more), with @kordinglab.bsky.social!
Applying new tools to entire brains, starting with C. elegans, offers the opportunity to uncover how molecules work together to generate neural physiology, and how neurons generate behavior, write @kordinglab.bsky.social and @eboyden3.bsky.social.
#neuroskyence
bit.ly/48EzEO8
#neuroskyence
bit.ly/48EzEO8
Whole-brain, bottom-up neuroscience: The time for it is now
Applying new tools to entire brains, starting with C. elegans, offers the opportunity to uncover how molecules work together to generate neural physiology and how neurons work together to generate…
bit.ly
October 21, 2025 at 12:38 AM
It was fun writing this essay, about bottom-up neuroscience and how we might simulate entire brains, using data collected via new technologies (expansion microscopy, optogenetics, whole brain voltage imaging, and more), with @kordinglab.bsky.social!
Reposted by Bill Mowrey
Reposted by Bill Mowrey
Comprehensive benchmarking of somatic single-nucleotide variant and indel detection at ultra-low allele fractions using short- and long-read data. #SNV #UltraLowFrequencyVariants #ShortRead #LongRead #Sequencing #Bioinformatics @biorxiv-bioinfo.bsky.social 🧬 🖥️
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Comprehensive benchmarking of somatic single-nucleotide variant and indel detection at ultra-low allele fractions using short- and long-read data
Mosaic mutations in normal tissues occur at low variant allele fractions (VAFs), complicating detection. To benchmark strategies, the SMaHT Network created a cell-line mixture (1:49) and produced…
www.biorxiv.org
October 19, 2025 at 6:05 PM
Comprehensive benchmarking of somatic single-nucleotide variant and indel detection at ultra-low allele fractions using short- and long-read data. #SNV #UltraLowFrequencyVariants #ShortRead #LongRead #Sequencing #Bioinformatics @biorxiv-bioinfo.bsky.social 🧬 🖥️
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Bill Mowrey
🎉 New preprint out!
"Removing genetic effects on plasma proteins enhances their utility as disease biomarkers"
We show that adjusting plasma proteins for genetic effects can make them stronger predictors of disease
👉 doi.org/10.1101/2025...
"Removing genetic effects on plasma proteins enhances their utility as disease biomarkers"
We show that adjusting plasma proteins for genetic effects can make them stronger predictors of disease
👉 doi.org/10.1101/2025...
October 16, 2025 at 9:16 PM
🎉 New preprint out!
"Removing genetic effects on plasma proteins enhances their utility as disease biomarkers"
We show that adjusting plasma proteins for genetic effects can make them stronger predictors of disease
👉 doi.org/10.1101/2025...
"Removing genetic effects on plasma proteins enhances their utility as disease biomarkers"
We show that adjusting plasma proteins for genetic effects can make them stronger predictors of disease
👉 doi.org/10.1101/2025...
Reposted by Bill Mowrey
In a paper just published in Nature Medicine, we characterised the largest cohort of people with loss-of-function mutations in the Melanocortin 4 receptor (MC4R) gene.
DOI: doi.org/10.1038/s415...
(1/6)
DOI: doi.org/10.1038/s415...
(1/6)
Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk - Nature Medicine
The authors explore the impact of MC4R deficiency on lipid metabolism in humans, based on two large cohorts. Findings indicate that individuals with obesity due to MC4R deficiency have lower cholester...
doi.org
October 16, 2025 at 11:18 AM
In a paper just published in Nature Medicine, we characterised the largest cohort of people with loss-of-function mutations in the Melanocortin 4 receptor (MC4R) gene.
DOI: doi.org/10.1038/s415...
(1/6)
DOI: doi.org/10.1038/s415...
(1/6)
For those of you at #ASHG2025 - I will be presenting at an ASHG Industry session today at 3 pm, “Synergizing complementary variant knowledge bases to advance rare disease diagnosis - an Industry Education Session Presented by Labcorp”. Come check it out and say hi!
October 15, 2025 at 12:11 PM
For those of you at #ASHG2025 - I will be presenting at an ASHG Industry session today at 3 pm, “Synergizing complementary variant knowledge bases to advance rare disease diagnosis - an Industry Education Session Presented by Labcorp”. Come check it out and say hi!
Reposted by Bill Mowrey
I’m pleased as punch to share our hot off the presses article in @ajhgnews.bsky.social : A scalable approach for genomic-first rare disorder detection in a healthcare-based population
Also presenting next week at #ashg25 #ashg2025
www.cell.com/ajhg/abstrac...
Also presenting next week at #ashg25 #ashg2025
www.cell.com/ajhg/abstrac...
A scalable approach for genomic-first rare disorder detection in a healthcare-based population
Beyond commonly screened disorders, genomic-first ascertainment of genetic disorders
remains underexplored. We developed a scalable framework for 2,701 additional rare
genetic disorders, identifying p...
www.cell.com
October 6, 2025 at 2:47 PM
I’m pleased as punch to share our hot off the presses article in @ajhgnews.bsky.social : A scalable approach for genomic-first rare disorder detection in a healthcare-based population
Also presenting next week at #ashg25 #ashg2025
www.cell.com/ajhg/abstrac...
Also presenting next week at #ashg25 #ashg2025
www.cell.com/ajhg/abstrac...
Reposted by Bill Mowrey
Over-transmission of NF1 mutant alleles in Neurofibromatosis type 1 https://www.medrxiv.org/content/10.1101/2025.10.06.25337162v1
October 10, 2025 at 8:58 PM
Over-transmission of NF1 mutant alleles in Neurofibromatosis type 1 https://www.medrxiv.org/content/10.1101/2025.10.06.25337162v1
Reposted by Bill Mowrey
15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵
October 10, 2025 at 4:47 PM
15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵
Reposted by Bill Mowrey
Our latest work is out in Nature today. In this paper, we introduce an improved version of NanoSeq, a duplex sequencing protocol with <5 errors per billion bp in single DNA molecules, and use it to study the somatic mutation landscape of oral epithelium in >1000 people www.nature.com/articles/s41...
Somatic mutation and selection at population scale - Nature
A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.
www.nature.com
October 8, 2025 at 4:31 PM
Our latest work is out in Nature today. In this paper, we introduce an improved version of NanoSeq, a duplex sequencing protocol with <5 errors per billion bp in single DNA molecules, and use it to study the somatic mutation landscape of oral epithelium in >1000 people www.nature.com/articles/s41...