Isaac García
@isaacgs94.bsky.social
Postdoctoral Fellow @ Sanger institute
Views are my own
Views are my own
Reposted by Isaac García
📣 Paper alert!
I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...
I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...
November 10, 2025 at 11:11 AM
📣 Paper alert!
I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...
I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...
New preprint from another part of my PhD! 📝👇
Some mutations arise after fertilisation 🧬, so early they can appear in both a parent’s body and their germ cells.
By analysing family trio genomes 👪, we built one of the largest catalogues of these “hidden” inherited variants yet.
tinyurl.com/mvns2ytv
Some mutations arise after fertilisation 🧬, so early they can appear in both a parent’s body and their germ cells.
By analysing family trio genomes 👪, we built one of the largest catalogues of these “hidden” inherited variants yet.
tinyurl.com/mvns2ytv
Landscape of parental postzygotic mutations in >11,000 rare disease trios
Postzygotic mutations (PZMs) arising post-fertilisation, prior to primordial germ cell specification, may be subsequently inherited by both somatic and germ cells, causing somatic mosaicism in the par...
tinyurl.com
October 28, 2025 at 11:04 AM
New preprint from another part of my PhD! 📝👇
Some mutations arise after fertilisation 🧬, so early they can appear in both a parent’s body and their germ cells.
By analysing family trio genomes 👪, we built one of the largest catalogues of these “hidden” inherited variants yet.
tinyurl.com/mvns2ytv
Some mutations arise after fertilisation 🧬, so early they can appear in both a parent’s body and their germ cells.
By analysing family trio genomes 👪, we built one of the largest catalogues of these “hidden” inherited variants yet.
tinyurl.com/mvns2ytv
Reposted by Isaac García
Interesting new @medrxivpreprint.bsky.social study, bearing on the interpretation of GWAS results:
“Common and rare genetic variants show network convergence for a majority of human traits” 🧪🧬
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
Common and rare genetic variants show network convergence for a majority of human traits
While both common and rare variants contribute to the genetic etiology of complex traits, whether their impacts manifest through the same effector genes and molecular mechanisms is not well understood...
www.medrxiv.org
June 29, 2025 at 7:49 AM
Interesting new @medrxivpreprint.bsky.social study, bearing on the interpretation of GWAS results:
“Common and rare genetic variants show network convergence for a majority of human traits” 🧪🧬
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
Reposted by Isaac García
This package is a game changer for population genetics. You can do pretty much all of the “usual” analyses, in R, and at a super fast speed 😍😍😍
So thanks mainly Evie and Andrea for creating this for all of us!
So thanks mainly Evie and Andrea for creating this for all of us!
We are excited to announce that tidypopgen – a new package for rapid population genetic workflows in R – is now available at evolecolgroup.github.io/tidypopgen/ 🧬💻 Read more in the preprint describing its features here: www.biorxiv.org/content/10.1... #popgen #Rpackage #genetics 1/2
Tidy Population Genetics
We provide a tidy grammar of population genetics, facilitating the manipulation and analysis of data on biallelic single nucleotide polymorphisms (SNPs). `tidypopgen` scales to very large genetic data...
evolecolgroup.github.io
June 20, 2025 at 12:56 PM
This package is a game changer for population genetics. You can do pretty much all of the “usual” analyses, in R, and at a super fast speed 😍😍😍
So thanks mainly Evie and Andrea for creating this for all of us!
So thanks mainly Evie and Andrea for creating this for all of us!
Reposted by Isaac García
New online! Making sense of the polygenicity of complex traits
Making sense of the polygenicity of complex traits
Nature Reviews Genetics, Published online: 16 June 2025; doi:10.1038/s41576-025-00866-7Hakhamanesh Mostafavi recalls a landmark paper by Boyle et al. on the omnigenic model, which proposed that complex traits are influenced by thousands of genes across the genome, including many that are only indirectly related to a trait through regulatory networks.
www.nature.com
June 16, 2025 at 12:30 PM
New online! Making sense of the polygenicity of complex traits
Reposted by Isaac García
Delighted that the 'flagship' manuscript on our @genesandhealth.bsky.social 44k exomes (British Pakistanis & Bangladeshis) is now preprinted. Great academic-industry collaboration. Lots of new associations (mostly additive, a few recessive) and new insights into homoz knockouts & drug discovery.
Preprint alert! 🚨
doi.org/10.1101/2025...
Our manuscript on Exome sequencing and analysis of 44,028 British South Asians, using @genesandhealth.bsky.social is now available at @medrxivpreprint.bsky.social!
We present several great results, and I’m thrilled to highlight the pieces I worked on:
doi.org/10.1101/2025...
Our manuscript on Exome sequencing and analysis of 44,028 British South Asians, using @genesandhealth.bsky.social is now available at @medrxivpreprint.bsky.social!
We present several great results, and I’m thrilled to highlight the pieces I worked on:
Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity
Genes and Health (G&H) is a biomedical study of adult British-Pakistani and -Bangladeshi research volunteers enriched for autozygosity. We performed whole exome sequencing in 44,028 G&H participants, ...
doi.org
June 12, 2025 at 7:14 PM
Delighted that the 'flagship' manuscript on our @genesandhealth.bsky.social 44k exomes (British Pakistanis & Bangladeshis) is now preprinted. Great academic-industry collaboration. Lots of new associations (mostly additive, a few recessive) and new insights into homoz knockouts & drug discovery.
Check out the new pre-print from Luci! 👇🏾 Super cool work highlighting the discovery of a blood biomarker of IBD! 👀🧬🔬
🚨 SUPER EXCITED to share our new preprint on the mucosal and circulatory immune landscape of Crohn’s disease!
🩸 Blood is commonly used in biomarker discovery and drug development, but how well does it reflect what's actually happening in the gut? 👀
🧵 1/10
🔗 www.medrxiv.org/content/10.1...
🩸 Blood is commonly used in biomarker discovery and drug development, but how well does it reflect what's actually happening in the gut? 👀
🧵 1/10
🔗 www.medrxiv.org/content/10.1...
Tissue-specific and circulatory immune signatures of mucosal inflammation in Crohn's disease
Crohn's disease (CD) is a heterogeneous disease characterized by chronic inflammation of the gastrointestinal tract driven by an aberrant immune response. To understand the immune mechanisms underlyin...
www.medrxiv.org
June 5, 2025 at 8:07 AM
Check out the new pre-print from Luci! 👇🏾 Super cool work highlighting the discovery of a blood biomarker of IBD! 👀🧬🔬
It's finally out people ✅🗞️! Check out the final version of our work exploring factors influencing the germline mutation rate and spectra on ~10,000 WGS family trios 🧬👨👩👦!
www.nature.com/articles/s41...
www.nature.com/articles/s41...
The impact of ancestral, genetic, and environmental influences on germline de novo mutation rates and spectra - Nature Communications
Here the authors analyze de novo mutations in >10,000 parent-offspring trios and find that ancestry and smoking independently associate with mutation rate, but that common genetic variants likely c...
www.nature.com
May 16, 2025 at 5:37 PM
It's finally out people ✅🗞️! Check out the final version of our work exploring factors influencing the germline mutation rate and spectra on ~10,000 WGS family trios 🧬👨👩👦!
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Isaac García
Our preprint describing and assessing the variant prioritisation approach for genomic newborn screening in the Generation Study @genomicsengland.bsky.social is now on medRxiv www.medrxiv.org/content/10.1...
Assessment of the variant prioritisation strategy for genomic newborn screening in the Generation Study
Purpose Genomic sequencing offers the opportunity to screen for hundreds of rare genetic conditions with a single test. To minimise potential negative impact on families and clinical services, it is c...
www.medrxiv.org
March 14, 2025 at 10:00 AM
Our preprint describing and assessing the variant prioritisation approach for genomic newborn screening in the Generation Study @genomicsengland.bsky.social is now on medRxiv www.medrxiv.org/content/10.1...
Reposted by Isaac García
We did it! We caught Starship #transposons moving between #fungal species in the lab, including between species separated by ~100my. We think Starships are a mediator of HGT in fungi, akin to conjugative elements in bacteria. Check out the preprint. www.biorxiv.org/content/10.1...
March 7, 2025 at 7:18 AM
We did it! We caught Starship #transposons moving between #fungal species in the lab, including between species separated by ~100my. We think Starships are a mediator of HGT in fungi, akin to conjugative elements in bacteria. Check out the preprint. www.biorxiv.org/content/10.1...
Reposted by Isaac García
Thrilled to share new work led by @jieyang437.bsky.social in the lab published today in @Nature. We find that Aspirin prevents metastasis by releasing T cells from immune suppression by platelet TXA2. @Cambridge_Uni @CRUKCamCentre rdcu.be/eci1U
March 5, 2025 at 6:56 PM
Thrilled to share new work led by @jieyang437.bsky.social in the lab published today in @Nature. We find that Aspirin prevents metastasis by releasing T cells from immune suppression by platelet TXA2. @Cambridge_Uni @CRUKCamCentre rdcu.be/eci1U
Reposted by Isaac García
Comparative analysis of human and mouse ovaries across age https://www.biorxiv.org/content/10.1101/2025.02.27.640481v1
March 3, 2025 at 8:34 PM
Comparative analysis of human and mouse ovaries across age https://www.biorxiv.org/content/10.1101/2025.02.27.640481v1
Reposted by Isaac García
I want to tell you a story about computers, creativity and art. (1/N) 🧵
Sydney Brenner once said in 2012 that “nobody has actually read the human genome. I mean, computers have processed the human genome, but we all know computers are stupid.”
(Summary of a talk I gave at the Sanger last week)
Sydney Brenner once said in 2012 that “nobody has actually read the human genome. I mean, computers have processed the human genome, but we all know computers are stupid.”
(Summary of a talk I gave at the Sanger last week)
March 3, 2025 at 2:56 AM
I want to tell you a story about computers, creativity and art. (1/N) 🧵
Sydney Brenner once said in 2012 that “nobody has actually read the human genome. I mean, computers have processed the human genome, but we all know computers are stupid.”
(Summary of a talk I gave at the Sanger last week)
Sydney Brenner once said in 2012 that “nobody has actually read the human genome. I mean, computers have processed the human genome, but we all know computers are stupid.”
(Summary of a talk I gave at the Sanger last week)
Reposted by Isaac García
Reposted by Isaac García
Contralateral cancers are an enigma: the unaffected organ is perfectly matched on exposures across life, yet despite this at older ages the risk of cancer in that organ is not much higher than a randomly selected organ from the same population. What can be happening? youtu.be/7rbsGpz9-XE
February 28, 2025 at 8:20 PM
Contralateral cancers are an enigma: the unaffected organ is perfectly matched on exposures across life, yet despite this at older ages the risk of cancer in that organ is not much higher than a randomly selected organ from the same population. What can be happening? youtu.be/7rbsGpz9-XE
Reposted by Isaac García
Really excited to share our next population-scale WGS work preprint. Here, we analyse three anthropometric traits in nearly 700,000 individuals (discovery UKB ~450K, replication AoU). We show, for these traits, that common and rare variant heritability is convergent
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations
Genetic association studies have mostly focussed on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we used whole-genome sequence (WGS) data in 672,...
www.biorxiv.org
February 26, 2025 at 4:11 PM
Really excited to share our next population-scale WGS work preprint. Here, we analyse three anthropometric traits in nearly 700,000 individuals (discovery UKB ~450K, replication AoU). We show, for these traits, that common and rare variant heritability is convergent
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Isaac García
We finally have some well-powered whole-genome heritability estimates, including a quasi-behavioral trait (BMI). For height, ~89% of the heritability estimated to reside in common variants. For BMI and WHR, ~100% estimated in common variants.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
February 26, 2025 at 6:25 PM
We finally have some well-powered whole-genome heritability estimates, including a quasi-behavioral trait (BMI). For height, ~89% of the heritability estimated to reside in common variants. For BMI and WHR, ~100% estimated in common variants.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Isaac García
Interesting new paper on links between male infertility and increased cancer risk from Maris Laan:
academic.oup.com/hropen/advan...
academic.oup.com/hropen/advan...
Significantly increased load of hereditary cancer–linked germline variants in infertile men
AbstractSTUDY QUESTION. What is the comparative load and profile of hereditary cancer–linked germline variants in infertile compared to fertile men?SUMMARY
academic.oup.com
February 25, 2025 at 8:12 PM
Interesting new paper on links between male infertility and increased cancer risk from Maris Laan:
academic.oup.com/hropen/advan...
academic.oup.com/hropen/advan...
Reposted by Isaac García
Excited to finally share that our paper looking at the effect of rare non-coding variants using WGS on circulating protein levels in the UKB has been released in Nature Genetics @naturegenet.bsky.social! We now analyse the full 3,000 circulating proteins in all 50,000 individuals rdcu.be/ea16i
Whole-genome sequencing analysis identifies rare, large-effect noncoding variants and regulatory regions associated with circulating protein levels
Nature Genetics - Rare variant association analysis of plasma proteins using whole-genome sequencing data in 54,306 individuals in the UK Biobank demonstrates that combining both single-variant and...
rdcu.be
February 24, 2025 at 6:26 PM
Excited to finally share that our paper looking at the effect of rare non-coding variants using WGS on circulating protein levels in the UKB has been released in Nature Genetics @naturegenet.bsky.social! We now analyse the full 3,000 circulating proteins in all 50,000 individuals rdcu.be/ea16i
Reposted by Isaac García
Quantitative genetics is poorly understood by many biologists, and that's surely a failure in how it is taught. But teaching biology as 'fundamentally complex' seems like one of the least promising educational ideas since those 1970s schools that made lessons optional.
www.cell.com/cell-systems...
www.cell.com/cell-systems...
Should biology put complexity first?
The dictum “Everything should be made as simple as possible, but no simpler” poses
a problem for biology. How simply can it be told without doing damage to its complex
nature? The answer might be foun...
www.cell.com
February 22, 2025 at 12:38 PM
Quantitative genetics is poorly understood by many biologists, and that's surely a failure in how it is taught. But teaching biology as 'fundamentally complex' seems like one of the least promising educational ideas since those 1970s schools that made lessons optional.
www.cell.com/cell-systems...
www.cell.com/cell-systems...
Reposted by Isaac García
I'm so happy that I can finally share the results of my first postdoc paper with @baym.lol!!! Turns out plasmids are an amazing system to study multi-scale evolution and we can track within-cell and between-cell dynamics!
(1/n) www.biorxiv.org/content/earl...
(1/n) www.biorxiv.org/content/earl...
Intracellular competition shapes plasmid population dynamics
Conflicts between levels of biological organization are central to evolution, from populations of multicellular organisms to selfish genetic elements in microbes. Plasmids are extrachromosomal, self-r...
www.biorxiv.org
February 21, 2025 at 8:36 PM
I'm so happy that I can finally share the results of my first postdoc paper with @baym.lol!!! Turns out plasmids are an amazing system to study multi-scale evolution and we can track within-cell and between-cell dynamics!
(1/n) www.biorxiv.org/content/earl...
(1/n) www.biorxiv.org/content/earl...
Reposted by Isaac García
Thrilled to share my 1st PhD's 1st publication at
@liigh-unam.bsky.social. Anecdotally it is also my 1st paper as corresponding author from my group / the "Paloegenomics and Evolutionary Biology". shorturl.at/VumOq Let us know what you think about it.
@liigh-unam.bsky.social. Anecdotally it is also my 1st paper as corresponding author from my group / the "Paloegenomics and Evolutionary Biology". shorturl.at/VumOq Let us know what you think about it.
Ancient DNA HLA typing reveals significant shifts in frequency in Europe since the Neolithic - Scientific Reports
Computational HLA typing has surged as a cost-effective strategy to uncover questions regarding the evolution of the HLA system, enabling immunogenic characterization from ancient DNA (aDNA) data. Nev...
shorturl.at
February 21, 2025 at 2:50 AM
Thrilled to share my 1st PhD's 1st publication at
@liigh-unam.bsky.social. Anecdotally it is also my 1st paper as corresponding author from my group / the "Paloegenomics and Evolutionary Biology". shorturl.at/VumOq Let us know what you think about it.
@liigh-unam.bsky.social. Anecdotally it is also my 1st paper as corresponding author from my group / the "Paloegenomics and Evolutionary Biology". shorturl.at/VumOq Let us know what you think about it.
Reposted by Isaac García
We are excited to announce a new faculty position here in Cambridge, for researchers in computational and/or theoretical biology, based jointly in Genetics and Mathematics. Come and join us! Happy to answer questions about research, teaching and working here. www.jobs.cam.ac.uk/job/50414/
Assistant/Associate Professor in Computational Biology - Job Opportunities - University of Cambridge
Assistant/Associate Professor in Computational Biology in the Department of Applied Mathematics and Theoretical Physics at the University of Cambridge.
www.jobs.cam.ac.uk
February 21, 2025 at 3:07 PM
We are excited to announce a new faculty position here in Cambridge, for researchers in computational and/or theoretical biology, based jointly in Genetics and Mathematics. Come and join us! Happy to answer questions about research, teaching and working here. www.jobs.cam.ac.uk/job/50414/
Reposted by Isaac García
Our lifestyle and environmental exposures are the predominant influencers of healthy aging and premature mortality, compared with polygenic risk, in the first comprehensive assessment
www.nature.com/articles/s41...
open-access
www.nature.com/articles/s41...
open-access
Integrating the environmental and genetic architectures of aging and mortality - Nature Medicine
Based on a systematic analysis of environmental exposures associated with aging and mortality in the UK Biobank, the relative contributions of such exposures and genetic risk for mortality and a range...
www.nature.com
February 19, 2025 at 2:37 PM
Our lifestyle and environmental exposures are the predominant influencers of healthy aging and premature mortality, compared with polygenic risk, in the first comprehensive assessment
www.nature.com/articles/s41...
open-access
www.nature.com/articles/s41...
open-access
Reposted by Isaac García
Our thymus, a critical source and trainer of T cells, involutes with aging. 2 new studies find a growth factor (FGF21) that delays involution (in mouse models) and may be a way to rejuvenate our immune system and promote healthy aging in the future.
February 19, 2025 at 2:53 PM
Our thymus, a critical source and trainer of T cells, involutes with aging. 2 new studies find a growth factor (FGF21) that delays involution (in mouse models) and may be a way to rejuvenate our immune system and promote healthy aging in the future.