Mykhaylo M. Malakhov
@mykmal.xyz
Genetic epidemiology postdoc at @stanford.edu
Thanks, those are good suggestions. I appreciate your words of encouragement.
January 25, 2026 at 7:29 PM
Thanks, those are good suggestions. I appreciate your words of encouragement.
Those issues are the most personal for me, but they are just the tip of the iceberg among the long list of things that are seemingly falling apart in the world. How is it possible to stay sane and continue focusing on research when so much else is at stake?
January 23, 2026 at 3:16 AM
Those issues are the most personal for me, but they are just the tip of the iceberg among the long list of things that are seemingly falling apart in the world. How is it possible to stay sane and continue focusing on research when so much else is at stake?
I wanted to keep this account focused on science, but it is hard to stay silent on political issues right now. My home country is still being bombed by Russia, the city I lived in for the past several years is under occupation by ICE, and the funding that supports my work is constantly threatened.
January 23, 2026 at 3:16 AM
I wanted to keep this account focused on science, but it is hard to stay silent on political issues right now. My home country is still being bombed by Russia, the city I lived in for the past several years is under occupation by ICE, and the funding that supports my work is constantly threatened.
🧵11/11 Finally, I want to extend a big thank you to Wei Pan for being my dissertation advisor and guiding me throughout this project. I am also grateful to @zkutalik.bsky.social and Guimin Gao for serving as peer reviewers and providing feedback that significantly strengthened this paper.
December 20, 2025 at 1:52 AM
🧵11/11 Finally, I want to extend a big thank you to Wei Pan for being my dissertation advisor and guiding me throughout this project. I am also grateful to @zkutalik.bsky.social and Guimin Gao for serving as peer reviewers and providing feedback that significantly strengthened this paper.
🧵10/11 Interested in trying out COWAS yourself? Our code is available at github.com/mykmal/cowas and weights for all models trained in this paper are provided at www.synapse.org/cowas.
GitHub - mykmal/cowas: Association testing for genetically regulated co-expression.
Association testing for genetically regulated co-expression. - mykmal/cowas
github.com
December 20, 2025 at 1:52 AM
🧵10/11 Interested in trying out COWAS yourself? Our code is available at github.com/mykmal/cowas and weights for all models trained in this paper are provided at www.synapse.org/cowas.
🧵9/11 By leveraging information from multiple proteins, COWAS also boosts power relative to standard PWAS. For example, alpha-synuclein (SNCA) did not attain significance for Parkinson's when tested on its own, but became significant once considered jointly with any one of several other proteins.
December 20, 2025 at 1:52 AM
🧵9/11 By leveraging information from multiple proteins, COWAS also boosts power relative to standard PWAS. For example, alpha-synuclein (SNCA) did not attain significance for Parkinson's when tested on its own, but became significant once considered jointly with any one of several other proteins.
🧵8/11 COWAS can also help to disentangle direct and interaction effects. For example, we found that APOE and its genetically regulated interaction with LDLR have opposite effects on Alzheimer's disease, which is consistent with known APOE biology. Standard PWAS was only able to identify APOE itself.
December 20, 2025 at 1:52 AM
🧵8/11 COWAS can also help to disentangle direct and interaction effects. For example, we found that APOE and its genetically regulated interaction with LDLR have opposite effects on Alzheimer's disease, which is consistent with known APOE biology. Standard PWAS was only able to identify APOE itself.
🧵7/11 Overall, COWAS uncovered dozens of interacting protein pairs with significant effects on disease risk. We identified many signals missed by standard PWAS, showing that co-expression may affect complex traits even if neither protein is detected to influence the trait when considered on its own.
December 20, 2025 at 1:52 AM
🧵7/11 Overall, COWAS uncovered dozens of interacting protein pairs with significant effects on disease risk. We identified many signals missed by standard PWAS, showing that co-expression may affect complex traits even if neither protein is detected to influence the trait when considered on its own.
🧵6/11 We applied COWAS to @ukbiobank.bsky.social proteomic data and the largest GWASs for LDL cholesterol, Alzheimer's disease, and Parkinson's disease. Although co-expression models had lower performance than single-protein models, we still obtained quality models for over 500 pairs for each trait.
December 20, 2025 at 1:52 AM
🧵6/11 We applied COWAS to @ukbiobank.bsky.social proteomic data and the largest GWASs for LDL cholesterol, Alzheimer's disease, and Parkinson's disease. Although co-expression models had lower performance than single-protein models, we still obtained quality models for over 500 pairs for each trait.
🧵5/11 Next, COWAS tests for association between genetically regulated co-expression and the trait of interest while also accounting for direct effects from each exposure. This joint model can be estimated using GWAS summary statistics, making our method just as easy to use as standard TWAS and PWAS.
December 20, 2025 at 1:52 AM
🧵5/11 Next, COWAS tests for association between genetically regulated co-expression and the trait of interest while also accounting for direct effects from each exposure. This joint model can be estimated using GWAS summary statistics, making our method just as easy to use as standard TWAS and PWAS.
🧵4/11 We developed the COWAS framework to answer this question. First, COWAS trains models to predict expression and co-expression from common genetic variants. In our main results we defined co-expression as the product of expression residuals, removing the linear genetic components of expression.
December 20, 2025 at 1:52 AM
🧵4/11 We developed the COWAS framework to answer this question. First, COWAS trains models to predict expression and co-expression from common genetic variants. In our main results we defined co-expression as the product of expression residuals, removing the linear genetic components of expression.
🧵3/11 This assumption can be a good approximation, but it ignores the effects of gene–gene or protein–protein interactions. Recent research has shown that interaction and co-expression effects are regulated by genetic variation. But how does genetically regulated co-expression affect complex traits?
December 20, 2025 at 1:52 AM
🧵3/11 This assumption can be a good approximation, but it ignores the effects of gene–gene or protein–protein interactions. Recent research has shown that interaction and co-expression effects are regulated by genetic variation. But how does genetically regulated co-expression affect complex traits?
🧵2/11 Most methods for identifying disease-relevant genes or proteins only consider one exposure at a time. TWAS trains gene-level models to predict expression from genetic variation and then tests each gene's imputed expression for association with an outcome trait. PWAS does the same for proteins.
December 20, 2025 at 1:52 AM
🧵2/11 Most methods for identifying disease-relevant genes or proteins only consider one exposure at a time. TWAS trains gene-level models to predict expression from genetic variation and then tests each gene's imputed expression for association with an outcome trait. PWAS does the same for proteins.
My second dissertation paper is now out in @natcomms.nature.com! Here we introduce the co-expression-wide association study (COWAS) method for identifying pairs of genes or proteins whose genetically regulated co-expression is associated with complex traits. 🧵⬇️
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Co-expression-wide association studies link genetically regulated interactions with complex traits - Nature Communications
Proteins can affect traits through their interactions with one another. Here, the authors propose the COWAS method to identify pairs of interacting genes or proteins whose genetically regulated co-exp...
www.nature.com
December 20, 2025 at 1:52 AM
My second dissertation paper is now out in @natcomms.nature.com! Here we introduce the co-expression-wide association study (COWAS) method for identifying pairs of genes or proteins whose genetically regulated co-expression is associated with complex traits. 🧵⬇️
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Mykhaylo M. Malakhov
GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult.
Our latest work on causal models for this is out yesterday:
www.nature.com/articles/s41...
A short🧵:
Our latest work on causal models for this is out yesterday:
www.nature.com/articles/s41...
A short🧵:
Causal modelling of gene effects from regulators to programs to traits - Nature
Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.
www.nature.com
December 11, 2025 at 5:54 PM
GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult.
Our latest work on causal models for this is out yesterday:
www.nature.com/articles/s41...
A short🧵:
Our latest work on causal models for this is out yesterday:
www.nature.com/articles/s41...
A short🧵:
Now we know what those sky-high APCs are being used for...
December 11, 2025 at 4:48 AM
Now we know what those sky-high APCs are being used for...
"The aim of equity is not to brag about how many students of a target background you awarded an A in calculus, it’s to ensure that every student actually learns."
This is such an important and timely article. I have noticed a lot of the same issues myself.
www.theargumentmag.com/p/when-grade...
This is such an important and timely article. I have noticed a lot of the same issues myself.
www.theargumentmag.com/p/when-grade...
When grades stop meaning anything
The UC San Diego math scandal is a warning
www.theargumentmag.com
November 23, 2025 at 4:51 PM
"The aim of equity is not to brag about how many students of a target background you awarded an A in calculus, it’s to ensure that every student actually learns."
This is such an important and timely article. I have noticed a lot of the same issues myself.
www.theargumentmag.com/p/when-grade...
This is such an important and timely article. I have noticed a lot of the same issues myself.
www.theargumentmag.com/p/when-grade...
Me too, especially if the paper has any mathematical notation in it.
November 8, 2025 at 3:05 PM
Me too, especially if the paper has any mathematical notation in it.
This is an exceedingly late post, but I wanted to share a few pictures from #IGES2025 earlier this fall. I had the honor of giving a platform talk on age-related genetic dysregulation, and I really enjoyed connecting with other researchers and exploring the beautiful city of Cologne!
November 7, 2025 at 11:09 PM
This is an exceedingly late post, but I wanted to share a few pictures from #IGES2025 earlier this fall. I had the honor of giving a platform talk on age-related genetic dysregulation, and I really enjoyed connecting with other researchers and exploring the beautiful city of Cologne!
More votes have been counted since then, and the updated map looks even better. There's not a single red cone across the whole state!
November 7, 2025 at 9:03 AM
More votes have been counted since then, and the updated map looks even better. There's not a single red cone across the whole state!
Reading papers detracts from time that could be spent actually analyzing data, and yet keeping up with new research is necessary to analyze data effectively. I'm still struggling to find a good balance, especially when I feel like I barely have enough time to read my email...
September 24, 2025 at 6:53 AM
Reading papers detracts from time that could be spent actually analyzing data, and yet keeping up with new research is necessary to analyze data effectively. I'm still struggling to find a good balance, especially when I feel like I barely have enough time to read my email...
Congratulations again on receiving the Williams Award for the best presentation by a student at IGES!! I really enjoyed meeting you and learning about your cool work!
September 3, 2025 at 12:05 PM
Congratulations again on receiving the Williams Award for the best presentation by a student at IGES!! I really enjoyed meeting you and learning about your cool work!
The use of dichotomized labels for traits that are actually continuous has bothered me ever since I started working on complex trait genetics. Sasha's blog post provides an excellent explanation of why this matters in the context of polygenic risk and embryo selection.
I wrote about how genetic risk works in the context of embryo selection and how people often think about it all wrong. A short 🧵:
What we talk about when we talk about risk
How embryo selection exploits our flawed intuitions about risk
open.substack.com
August 10, 2025 at 7:33 PM
The use of dichotomized labels for traits that are actually continuous has bothered me ever since I started working on complex trait genetics. Sasha's blog post provides an excellent explanation of why this matters in the context of polygenic risk and embryo selection.
Yesterday I successfully defended my dissertation! It feels surreal to finally reach the end of my PhD journey at @umnsph.bsky.social. Thank you to my adviser Wei Pan and to my committee members @elock.bsky.social, @aazaidi.bsky.social, and Thierry Chekouo for your invaluable mentorship and support!
July 24, 2025 at 9:24 PM
Yesterday I successfully defended my dissertation! It feels surreal to finally reach the end of my PhD journey at @umnsph.bsky.social. Thank you to my adviser Wei Pan and to my committee members @elock.bsky.social, @aazaidi.bsky.social, and Thierry Chekouo for your invaluable mentorship and support!