Saori Sakaue @saorisakaue Twitter profile | Pikagi

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Saori Sakaue

@saorisakaue

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Instructor @harvardmed | Incoming Assistant Professor @uwgenome | Seeking how much of our destiny can be explained by data and science.

Brookline, MA

https://t.co/3zqQDXlAlV

Joined September 2019

Don't wanna be here? Send us removal request.

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@saorisakaue

Saori Sakaue

4 months

Beyond thrilled to announce that I will be starting my research group at Genome Sciences at the University of Washington @UW next spring💫💫My dream place to do genetics & genomics, and such an exciting timing with a lot of new technologies and large-scale datasets emerging! (1/)

@uwgenome

UW Genome Sciences

4 months

Genome Sciences is pleased to announce that Dr. Saori Sakaue and Dr. William DeWitt have accepted our offers to join the department as assistant professors!

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@saorisakaue

Saori Sakaue

1 year

Anyone who wants to study #HLA but feels hesitant as HLA is too complicated☹️? Happy to share our paper @NatureProtocols describing the up-to-date knowledge on HLA #genetics and step-by-step tutorial for HLA imputation and association with @soumya_boston 🥳

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Tutorial: a statistical genetics guide to identifying HLA alleles driving complex disease

Nature Protocols - This tutorial provides guidelines for imputing human leukocyte antigen alleles, including standard quality control measures for input genotyping data and best practice...

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@saorisakaue

Saori Sakaue

3 years

Genetic study needs diversity!🌎 Hugely glad and grateful to see our mammoth genetic study, 220 human phenotypes, 3 populations, 50M health records, and 5K novel loci, published now in Nature Genetics @NatureGenet !🥳🎉✌️ Here are 🧵

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@saorisakaue

Saori Sakaue

3 years

Have you ever heard of a mysterious region called "killer immunoglobulin-like receptor (KIR)", which is critical for innate #immunity ?🧐We analyzed this complex region by deep target sequencing and devising a new #bioinformatics tool @CellGenomics !

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@saorisakaue

Saori Sakaue

2 years

Preprint alert📣📣Excited to share our new method SCENT to create accurate enhancer-gene map from #singlecell #multiome data with @soumya_boston ! SCENT using multiome technology is very powerful in defining disease causal variants & genes in #GWAS #ASHG22

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@saorisakaue

Saori Sakaue

2 years

Anyone interested in studying HLA in human diseases?📣📣 We (with @soumya_boston ) put our love❤️ in HLA into this manuscript describing a thorough protocol for genetic study of HLA, including a step-by-step tutorial for HLA imputation and many statistical methods for association!

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@biorxiv_genetic

bioRxiv Genetics

@biorxiv_genetic

2 years

A statistical genetics guide to identifying HLA alleles driving complex disease #biorxiv_genetic

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@saorisakaue

Saori Sakaue

4 years

New release and #ASHG20 alert!🧬We are excited to present our 220 deep phenotype GWAS in BioBank Japan, by incorporating 50M health records and 7M medication record, with @masakanai and @okada_yukinori . This vastly expands an atlas of genetic association in non-Europeans. (1/n)

@GWAS_lit

GWAS_lit

4 years

A global atlas of genetic associations of 220 deep phenotypes

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@saorisakaue

Saori Sakaue

7 months

Hot off the press!🔥We tackled the challenge of defining causal variants and genes in complex diseases by #GWAS and single-cell multiomics. Delighted that our statistical method SCENT is now published in @NatureGenet with @soumya_boston ✨⭐️ Tweetorial👇

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Tissue-specific enhancer–gene maps from multimodal single-cell data identify causal disease alleles

Nature Genetics - SCENT is a nonparametric method that models association between chromatin accessibility and gene expression in single-cell multimodal datasets, enabling construction of...

@saorisakaue

Saori Sakaue

2 years

Preprint alert📣📣Excited to share our new method SCENT to create accurate enhancer-gene map from #singlecell #multiome data with @soumya_boston ! SCENT using multiome technology is very powerful in defining disease causal variants & genes in #GWAS #ASHG22

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@saorisakaue

Saori Sakaue

5 years

Delighted to see our paper out in @NatureMedicine with @masakanai @dalygene @okada_yukinori . We show the novel utility of polygenic risk scores in 680K people in BioBank Japan @uk_biobank and @FinnGen_FI . I do hope science goes on!

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Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores...

Nature Medicine - Cross-biobank analysis reveals that polygenic risk scores (PRS) for hypertension and obesity are associated with shorter lifespan, serving as a proof-of-principle that PRS could...

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@saorisakaue

Saori Sakaue

3 years

We made it to the @NatureGenet cover😆🎉😊Thanks to a secret team for this image @kei_toon @Hirofumi_Seo_ @masakanai @okada_yukinori !! An ukiyoe with 3 origami cranes facing each other representing global pops, highlighting the importance of cross-pop collab in human genetics🧬

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@saorisakaue

Saori Sakaue

3 years

Genetic study needs diversity!🌎 Hugely glad and grateful to see our mammoth genetic study, 220 human phenotypes, 3 populations, 50M health records, and 5K novel loci, published now in Nature Genetics @NatureGenet !🥳🎉✌️ Here are 🧵

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@saorisakaue

Saori Sakaue

2 years

#ASHG22 📣📣Today I am super excited to present our new statgen method to create accurate enhancer-gene map from #singlecell #multiome data! I’ll show how it is powerful in fine mapping disease alleles in #GWAS 🙂Join us at 10:45am Room515!!🙌

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@saorisakaue

Saori Sakaue

4 years

📣Data Release Alert📣 On our 220 cross-pop deep-phenotype GWAS project, I have compiled all 220*3 GWAS summary statistics, and Super @masakanai deployed them into the beautiful web portal!! You can search and download everything at 🧵

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@GWAS_lit

GWAS_lit

4 years

A global atlas of genetic associations of 220 deep phenotypes

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@saorisakaue

Saori Sakaue

4 years

Happy to share our #GWAS on #RareDiseases out today at @NatureComms with @okada_yukinori ! We performed the first GWAS on pulmonary alveolar proteinosis, a severe lung disease with prevalence of 6/M, and showed an association with common variation in #HLA .

Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis

Nature Communications - Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association...

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@saorisakaue

Saori Sakaue

5 years

Excited to present our work on PRS and lifespan with @masakanai @dalygene @okada_yukinori . To translate genetics into improving human health beyond mapping of GWAS variants, we explored PRS associations with lifespan in 676K people of BioBank Japan, @uk_biobank and @FinnGen_FI .🧬

@biorxiv_genetic

bioRxiv Genetics

@biorxiv_genetic

5 years

Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan #biorxiv_genetic

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@saorisakaue

Saori Sakaue

5 years

Why did we East Asians evolve to be intolerant to alcohol? We are glad to provide some hints to this question!🍷

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@saorisakaue

Saori Sakaue

2 years

Our latest GWAS paper for rheumatoid arthritis and exciting stories about each locus we discovered (e.g., sQTL by long-read RNA-seq, TFs, disease prediction etc.) are now out in @NatureGenet !🥳 We recommend using this latest summary statistics for your genetic analyses📣

@Kazu_Ishigaki

Kazuyoshi Ishigaki

2 years

Thrilled to share our manuscript on multi-ancestry GWAS of rheumatoid arthritis published today in @NatureGenet !! This work is enabled by massive support from many including @soumya_boston , @okada_yukinori , @saorisakaue , @ChikashiTerao

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@saorisakaue

Saori Sakaue

4 years

Moving forward, I have started my new journey as a postdoc here at beautiful autumn Boston🍁 @harvardmed with @soumya_boston !! I want to thank everyone who made this transition possible despite many many difficulties in the middle of pandemic.

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@saorisakaue

Saori Sakaue

3 years

During my short visit to Japan last month, I was able to attend this sweet award ceremony of L'Oréal-UNESCO For Women in Science Award💐 Thank you @LOrealGroupe @UNESCO for encouraging us #WomenInSTEM and I deeply appreciate all my mentors past and present for bringing me here.

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@saorisakaue

Saori Sakaue

5 years

Pleased to present our work on the fine-scale genetic diversity in Japan, UK, Malay, and Arab now out in @NatureComms with @okada_yukinori . If interested, please have a look at Introduction on human history! (1/5)

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Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences...

Nature Communications - Population structure, even subtle differences within seemingly homogenous populations, can have an impact on the accuracy of polygenic prediction. Here, Sakaue et al. use...

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@saorisakaue

Saori Sakaue

5 years

Our work on GWASs for 42 diseases in 212,453 Japanese is now on @biorxivpreprint . A great resource of non-European disease-focused genetic association! I always respect @Kazu_Ishigaki for the incredible amount of work and his passion.

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Large scale genome-wide association study in a Japanese population identified 45 novel susceptibi...

The overwhelming majority of participants in current genetic studies are of European ancestry[1][1]–[3][2], limiting our genetic understanding of complex disease in non-European populations. To...

www.biorxiv.org

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@saorisakaue

Saori Sakaue

11 months

I am so honored to receive this wonderful Award from Broad Institute @broadinstitute ✨ Grateful for warm & great mentorship from @soumya_boston and all my colleagues who led me here.

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@saorisakaue

Saori Sakaue

3 years

We (with super @masakanai !) created a web portal to distribute all summary statistics. GWAS catalog @GWASCatalog will also host the statistics soon! Please explore, enjoy, and use the data for your research!

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@saorisakaue

Saori Sakaue

3 years

With 5.4 million individuals, we finally (!) see some saturation of signals in height GWAS, but this is not the end of our journey in genetics🧬Quite delighted to join and share this excitement🙂

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@joelhirschhorn

Joel Hirschhorn

@joelhirschhorn

3 years

Excited that the GIANT consortium height GWAS: A Saturated Map of Common Genetic Variants Associated with Human Height from 5.4 Million Individuals of Diverse Ancestries is on biorxiv! Great effort from 100s of investigators and GIANT height working group,

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@saorisakaue

Saori Sakaue

3 years

In case you missed this, this is our largest and most diverse #GWAS ever for rheumatoid arthritis, a representative common complex autoimmune disease. I especially want to feature an exciting functional insight with long-read RNA-seq. Summary stats are already available for you🙂

@Kazu_Ishigaki

Kazuyoshi Ishigaki

3 years

Thrilled to share our latest manuscript on large-scale trans-ancestry GWAS of rheumatoid arthritis: . This work is enabled by great support from researchers worldwide, @saorisakaue , @ChikashiTerao , @yluo86 , @okada_yukinori , and @soumya_boston .

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@saorisakaue

Saori Sakaue

11 months

Hot off the press!! ✨ Our approach to map genetic effect on #HLA expression at single-cell resolution! Congrats Joyce for her brave undertaking of this challenge🥳

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Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution

Nature Genetics - scHLApers is an analysis pipeline that quantifies single-cell expression of HLA genes using a personalized genomic reference. Mapping of HLA expression quantitative trait loci at...

@joycebkang

Joyce Kang, PhD

11 months

Excited that our single-cell eQTL study of HLA genes is out now in @NatureGenet ! ⭐️ Huge thx to @soumya_boston @saorisakaue @yluo86 for their guidance Check out this great News & Views by the Gaffney lab describing the key points:

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@saorisakaue

Saori Sakaue

3 years

My recent talk on cross-population #genetic study for medicine at wonderful @ICDAbio Scientific Plenary is now available on YouTube!📽️ Please enjoy and I welcome any feedback☺️ #GWAS #diversity

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ICDAbio Virtual Scientific Plenary 2022: Plenary 1B_Genetic Maps for...

Virtual Scientific Plenary 2022: Plenary 1B Genetic Maps for M2M2M Speakers: Nancy Cox (Moderator)Hernán Dopazo: PoblAR: The Population Genome Reference Biob...

www.youtube.com

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@saorisakaue

Saori Sakaue

2 years

Interested in genotype imputation and how you can easily do it at Michigan Imputation Server?🧐We have a seminar at the Genetics and Genomics Digital Forum @GeneticsSociety tomorrow at 8:30 EST! All #ASHG22 participants are free upon registration🥳I'll talk about HLA imputation🙂

@umimpute

Michigan Imputation Server

2 years

How does the imputation server work? What’s new? Join us on Nov 15 @ for a deep dive. @lukfor @seppinho Xueling Sim @saorisakaue @avsmith and Christian Fuchsberger are excited to answer all your questions. #ASHG22

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@saorisakaue

Saori Sakaue

26 days

Tomorrow!📣

@varianteffects

Atlas of Variant Effects Alliance

@varianteffects

1 month

📌🗓️Coming up on October 1st, 2024 with Saori Sakaue ( @saorisakaue @broadinstitute @harvardmed Incoming Assistant Professor @uwgenome ) and Priyanka Bajaj ( @Priyank67495046 @UCSF ) ℹ️

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@saorisakaue

Saori Sakaue

2 years

How are cell populations in swollen joints epigenetically regulated?🧐 Here we present a chromatin atlas of synovial tissues from inflamed joints in rheumatoid arthritis patients! 🎨 Incl. single-cell ATAC-seq and single-cell multiome RNA/ATAC-seq data📢

@soumya_boston

Soumya Raychaudhuri সৌম্য রায়চৌধুরী

2 years

So excited to share our #RheumatoidArthritis tissue chromatin atlas of 87K cells from 30 individuals! With, @soumya_boston , @saorisakaue , @aparnanathan , @Donlinlab , Kevin Wei and #AMP -RA! @NIH_NIAMS . (Tweeting on behalf of the talented Kathryn Weinand)

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@saorisakaue

Saori Sakaue

4 years

We conducted trans-biobank meta-analysis with @uk_biobank and @FinnGen_FI , confirmed replication and discovered over 4K novel association loci. We are so grateful to this opportunity for collaboration @dalygene @APalotie (2/n)

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@saorisakaue

Saori Sakaue

3 years

The pipeline and the reference data are available here! Thank you for all the people helping me tackle this extremely complex and diverse region exp. Dr. Hosomichi, Dr. Inoko and @okada_yukinori 😌

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GitHub - saorisakaue/KIR_project

Contribute to saorisakaue/KIR_project development by creating an account on GitHub.

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@saorisakaue

Saori Sakaue

4 years

I also contributed to the logo design of with a flavor of Japanese Origami and Kimono🙂✌️

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@saorisakaue

Saori Sakaue

4 years

After plenary and before happy hour🍺, are you interested in mystery of alcohol🍷 and positive selection in East Asians? Please visit our invited session 037 "Evolutionary Genomic Medicine" where we discuss an intersection between evolution and complex traits at 3:30pm! #ASHG20

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@saorisakaue

Saori Sakaue

5 years

Another work from our collab is out today! While Europeans have evolved to be taller, it does't seem to be the case in Japanese. I learned so many things from the first author Masato ( @masato__AKIYAMA ). Congrats💐

Characterizing rare and low-frequency height-associated variants in the Japanese population

Nature Communications - Thousands of genetic loci are known to associate with human height, but these are mainly based on studies in European ancestry populations. Here, Akiyama et al. construct a...

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@saorisakaue

Saori Sakaue

3 years

Good thing about collaborative biobank analyses is that we can harmonize phenotypes across populations. We did GWAS of the same phenotypes in UK Biobank @uk_biobank and FinnGen @FinnGen_FI , enabling systematic comparison and meta-analysis (5K novel loci!)

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@saorisakaue

Saori Sakaue

4 years

Finally we performed a matrix decomposition of these sumstats, integrated with metabolome and epigenetics data, and suggested a hypothesis-free genetic support of current disease classifications and underlying biology. Thanks so much @yk_tani @manuelrivascruz !! (4/n)

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@saorisakaue

Saori Sakaue

2 years

We developed a new statistical method "SCENT" to carefully model association between sparse ATAC-seq and sparse RNA-seq matrices by Poisson regression and bootstrapping. We define accurate enhancer-gene links at single-cell resolution with well controlled type-1 error!

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@saorisakaue

Saori Sakaue

3 years

Sometimes we can explain complex trait genetics by combination of more simple genetics of biomarkers/metabolites. For example, heart disease genetics was explained by component 2, and this component 2 was projected into the genetics of blood pressure and lipids!

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@saorisakaue

Saori Sakaue

3 years

Pleiotropy and polygenicity are pervasive throughout the genome. We found that the architecture of pleiotropy is similar between Europeans and East Asians. #MHC is associated with many traits as expected, so we performed comprehensive HLA-fine-mapping with a lot of novel asscs.

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@saorisakaue

Saori Sakaue

5 years

Are you interested in what strongly affects our lifespan and how we addressed this question with genetics and global biobanks? Please come to my talk today at Session 30, Grand Ballroom C, 5:30PM #ASHG19 !🧬 I thank @masakanai , @dalygene , @okada_yukinori and all the collaborators.

@okada_yukinori

YukinoriOkada

@okada_yukinori

5 years

Our platform talks at ASHG2019. (1) PgmNr 63 (Wed). Sakaue S, Kanai M. “Trans-ethnic mega-biobank PRS analysis involving 676,000 individuals identified blood pressure and obesity as causal drivers affecting human longevity.” #ASHG2019 #PolygenicRiskScore #PrecisionMedicine

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@saorisakaue

Saori Sakaue

7 months

Thank you for all the colleagues & reviewers who helped us improve this project and let me find a lot of unexpected discoveries along the way!😊 Freely accessible paper link: Github:

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GitHub - immunogenomics/SCENT: Single-Cell ENhancer Target gene mapping using multimodal data with...

Single-Cell ENhancer Target gene mapping using multimodal data with ATAC + RNA - immunogenomics/SCENT

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Saori Sakaue

3 years

Looking forward to this Plenary to learn exciting progress in #genetics #GWAS #biobank #V2F #M2M2M and more! Registration free and open📣

@ICDAbio

International Common Disease Alliance

3 years

We’re thrilled to share the agenda and open registration () for #ICDAbio Virtual Scientific Plenary (Mar 8-9)! #ICDAbio2022

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@saorisakaue

Saori Sakaue

4 years

Very importantly, we are now preparing for finalizing the official release of all summary statistics with super-talented @masakanai for accelerating further collaborations🙂!! Stay tuned, please enjoy, and we appreciate comments and feedbacks! (5/5)

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Saori Sakaue

2 years

The largest ever GWAS in 5.4 million people for height is out today👏The gene discovery may be finally saturated for Europeans, but diverse ancestry has a potential to discover more.

@LoicYengo

Loïc Yengo

2 years

We are pleased to announce that our height GWAS: A Saturated Map of Common Genetic Variants Associated with Human Height is published in @Nature today! This is a fantastic effort involving >600 GIANT consortium investigators and @23andMe .

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Saori Sakaue

1 year

@umimpute In case you'd like to watch it on youtube📽️, I did a seminar @broadinstitute MPG Primer that goes through the main topics of the paper! Check it out here✨:

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MPG Primer: A statistical genetics guide to identifying HLA alleles...

March 30, 2023Medical and Population Genetics PrimerBroad Institute of MIT and HarvardSaori SakaueBroad InstituteHarvard Medical SchoolA statistical genetics...

www.youtube.com

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@saorisakaue

Saori Sakaue

4 years

For lovers of extreme p values @Eric_Fauman , we've got you covered! Apologies for not being able to plot infinity at Manhattan plots, but I did check that there is NO P=ZERO in all downloadable summary statistics! We've got a extreme P of 3.1e-26677 at rs35754645 with Bilirubin!

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@saorisakaue

Saori Sakaue

2 years

Overall, our project showcases the high utility of #singlecell #multimodal data to define causal variants and assign function to disease variants ( #V2F )! A statistical model we used is available at GitHub and we are happy to hear your feedback!!😀 (/end)

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GitHub - immunogenomics/SCENT: Single-Cell ENhancer Target gene mapping using multimodal data with...

Single-Cell ENhancer Target gene mapping using multimodal data with ATAC + RNA - immunogenomics/SCENT

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@saorisakaue

Saori Sakaue

3 years

To tackle this, we decomposed Z score matrix of 159 disease GWAS by SVD and derived 40 orthogonal components. Then we tried to annotate those simple components biologically by integrating with biomarker, metabolomics GWAS and epigenetics data. Thank you @yk_tani @manuelrivascruz

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@saorisakaue

Saori Sakaue

4 months

My lab will use and develop statistical genetics tools that integrate these molecular data to improve the resolution🔬 of our understanding of disease mechanisms, ultimately for improved patient care some day (2/)

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@saorisakaue

Saori Sakaue

5 years

Have you ever wondered how finely we can distinguish population substructures by our genome? The result in Japanese is really surprising🧬! I will talk again as a replacer(!) at Session52,Grand Ballroom C,11:45AM #ASHG19 . Please come join the discussion👍

@okada_yukinori

YukinoriOkada

@okada_yukinori

5 years

Our platform talks at ASHG2019. (2) PgmNr 171 (Thu). Hirata J, Sakaue S. “ML-based deconvolution of biobank-driven GWAS data with 170k individuals enlightens the finest-scale genetic, evolutional, and PRS divergence within Japanese.” #ASHG2019 #PolygenicRiskScore #machinelearning

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Saori Sakaue

1 year

Free access to the paper: We have an accompanying website with example codes for GWAS QC, HLA imputation and association tests, hoping that they are helpful for those who just started to look into the HLA locus😉

GitHub - immunogenomics/HLA_analyses_tutorial: A thorough tutorial on HLA imputation and associat...

A thorough tutorial on HLA imputation and association, accompanying our manuscript "Tutorial: A statistical genetics guide to identifying HLA alleles driving complex disease" - im...

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@saorisakaue

Saori Sakaue

4 years

We found that the architecture of pleiotropy is similar between Europeans and East Asians!! (An exciting result for me). MHC is associated with many traits as expected, so we performed comprehensive HLA-finemapping. (3/n)

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@saorisakaue

Saori Sakaue

3 years

Marginal effect sizes are mostly concordant between Europeans and Japanese, but sometimes different, suggesting possible differences in biology, environment, LD, or MAF? We were really glad to see this paper @mathiesoniain diving into our results!

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@saorisakaue

Saori Sakaue

3 years

We analyzed the BioBank Japan genotype data (180K) with deep diving electronic health records, and conducted GWAS for 220 phenotypes which substantially contributed to expand the atlas of genetic associations in Non-Europeans.

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@saorisakaue

Saori Sakaue

4 years

Please enjoy and use these data for your research and drop us a line for any potential collaborations! Huge thanks to the amazing resources from BioBank Japan, @RIKEN_IMS @uk_biobank @FinnGen_FI @okada_yukinori @dalygene @APalotie

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@saorisakaue

Saori Sakaue

5 years

Heading from Tokyo to Houston to attend #ASHG19 ✈️So thrilled with my presentation at Excellence in Genetics Awards Reception on Tue and platform talk on Wed! Grateful to all the collaborators and my great mentor @okada_yukinori for this opportunity😃

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Saori Sakaue

3 years

The decompose components recapitulated the current disease classifications defined by ICD10 framework. And more interestingly...

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@saorisakaue

Saori Sakaue

4 months

I want to take a moment to deeply thank all my mentors/colleagues/friends past and present who keep encouraging me and motivate me😌, especially immense support from current advisor @soumya_boston along my scientific journey!! (3/3)

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@saorisakaue

Saori Sakaue

2 years

#GWAS has been hugely successful, but a major challenge in genetics is now to define disease causal variants and genes identified through GWAS. It has been challenging due to complex LD structure and non-coding mechanisms of 90% loci we discovered..

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@saorisakaue

Saori Sakaue

3 years

I would like to appreciate all people involved in this study for global collaborations in the middle of pandemic, especially my previous mentor @okada_yukinori , a great colleague @masakanai , @yk_tani , @manuelrivascruz , @dalygene , @APalotie , and all biobanks' participants😌 (fin.)

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@saorisakaue

Saori Sakaue

3 years

We also tried fine-tuned classification of similar diseases by these components. We grouped allergic diseases into axis 1 (e.g., asthma) and axis 2 (contact dermatitis), and interestingly, these axes recapitulated historically classified two types of hypersensitivity reactions.

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@saorisakaue

Saori Sakaue

5 years

I am so amazed with this article on a scientist who has been counting California butterflies for 47 years...! Q. “Why butterflies?” A. “Why not?” I want to seek my own butterflies🦋

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Meet the scientist who's been counting California butterflies for 47 years and has no plans to stop

A UC Davis professor's simple mission: Record and identify every butterfly he sees. What he’s discovered has disturbed him.

www.latimes.com

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@saorisakaue

Saori Sakaue

5 years

Thanks everyone who answered my question! For those who want to know our findings further, our abstract is now officially press released by ASHG @GeneticsSociety ! #ASHG19

@GeneticsSociety

ASHG

@GeneticsSociety

5 years

#ASHG19 press release: Beyond signaling risk, blood pressure and obesity causally related to lifespan. #bloodpressure #obesity #lifespan #genetics #risk

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@saorisakaue

Saori Sakaue

2 years

More excitingly😉, SCENT enhancers are dramatically enriched in causal variants for disease loci from #GWAS . We showed this by using fine-mapping results in two large-scale biobanks, #FinnGen and #UKBiobank . SCENT also outperformed popular bulk-based enhancer-gene maps!!👏

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@saorisakaue

Saori Sakaue

2 years

But given GWAS causal variants are highly enriched in gene regulatory variants, accurate enhancer-gene map will help us identify both causal variants and genes.

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@saorisakaue

Saori Sakaue

2 years

Beyond common diseases, we show SCENT can also prioritize causal variants & genes for #Mendelian #RareDisease and for non-coding somatic mutations in cancers. SCENT is a versatile method to find causal mechanisms for many kinds of human diseases!

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@saorisakaue

Saori Sakaue

3 years

We hope our study will be another starting place to nail down to the biology through genetics, and provide a way to improve treatment for patients (as I am a physician-geneticist)! Last but not least...

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@saorisakaue

Saori Sakaue

11 months

In case you missed this, we developed a very scalable & robust statistical method to detect how our genotype🧬 changes our granular cell state compositions in our blood💉 Congrats Laurie, and check out our manuscript & github!

@LaurieRumker

Laurie Rumker

1 year

We are excited to share Genotype-Neighborhood Associations, GeNA, a new tool adapting our CNA framework to detect cell states associated in abundance with genetic variants at genome-wide scale in high-dimensional single-cell data w/ @soumya_boston 🧵

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@saorisakaue

Saori Sakaue

3 years

Finally, what can we learn about biology and medicine💊? Isn’t it great if we can explain complex disease genetics by combination of more simple traits, or if we can optimize current disease classifications through the eyes of genetics?

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@saorisakaue

Saori Sakaue

3 years

SharedIt link:

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@saorisakaue

Saori Sakaue

3 years

@towfiqueRaj @lopeskp @ricardovialle @RushUniversity Congrats @lopeskp @ricardovialle @towfiqueRaj !!

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@saorisakaue

Saori Sakaue

4 years

@joycebkang Looks like a great tutorial!!🎉

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Saori Sakaue

2 years

However, currently used enhancer-gene maps (e.g. EpiMap, ABC model) are mostly from bulk-tissue data, obscuring tissue-specific and cell-type-specific gene regulation. You may not find your-disease-relevant enhancer-gene map in the currently available datasets...

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@saorisakaue

Saori Sakaue

3 years

@cristenw @Eric_Fauman In our study, CDKN2B-AS1 was among the loci with the highest degree of pleiotropy, and mostly driven by cardiovascular phenotypes!

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@saorisakaue

Saori Sakaue

4 years

@Eric_Fauman @masakanai @gem_epi @NanaMatoba rs671 has significantly larger effect sizes in men for almost all traits we investigated!

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@saorisakaue

Saori Sakaue

3 years

@martinmaiers @PN0rmski @jillahjillah @mjwsim @CellGenomics @ParhamLab Thank you all of you for all the great works in this field, which inspired us hugely!😀👏

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@saorisakaue

Saori Sakaue

2 years

Our method showed higher precision in capturing causal variants for eQTLs than previous single-cell peak-gene linkage methods (Signac and ArchR) which use linear regression and may not be designed for prioritizing causal variants..

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@saorisakaue

Saori Sakaue

2 years

So we used single-cell mutimodal RNA/ATAC-seq datasets (e.g., 10X Multiome/SHARE-seq) in thousands of cells, instead of hundreds of samples, to define accurate and cell-type-specific enhancer-gene map! You can easily create your-own-map once you get tissues of disease relevance😀

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@saorisakaue

Saori Sakaue

1 year

Quick HLA imputation can be easily performed at Michigan Imputation Server @umimpute with the most recent multi-ancestry HLA imputation reference panel📢 !

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@saorisakaue

Saori Sakaue

4 years

Go Masa!!

@masakanai

Masahiro Kanai

4 years

In #ASHG20 Plenary Session today, I’m excited to talk about our work to fine-map causal variants across diverse pops! Great collaborative effort across Biobank Japan @FinnGen_FI and @uk_biobank with mentorship from Hilary Finucane @dalygene @okada_yukinori

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@saorisakaue

Saori Sakaue

3 years

@Eric_Fauman @masakanai We imputed the GWAS data using pop-specific+1KG ref panel (total n = 3541, 7082 haplotypes). After all 220 GWASs were done, I went through fun eyeballing of all novel loci😅, and my impression was that too rare variants such as MAF < 0.1% sometimes look

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@saorisakaue

Saori Sakaue

2 years

@trizzlor Really a great question! We wondered the similar thing and confirmed that the higher causal variant enrichment in SCENT peaks was maintained (1) when we excluded promoters from analyses and (2) after we matched TSS-distance between SCENT and non-SCENT peaks. (Suppl Fig 6a-c)🙂

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@saorisakaue

Saori Sakaue

2 years

@trizzlor Thanks! That may be due to the smaller amount of false-positive enhancer-gene links in our method. We found highly inflated statistics if we just did linear regression/correlation in the null simulated data which are commonly used in previous softwares even when data are sparse.

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@saorisakaue

Saori Sakaue

2 years

@anshulkundaje I fully agree with this idea, and I am also curious to know what exactly the method effects and the data type effects are. We'd hope we may be able to do this benchmarking in the IGVF consortium🙂

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@saorisakaue

Saori Sakaue

3 years

@Eric_Fauman @masakanai interesting and biologically reasonable but not always, as might have been expected from the # haplotypes we used in the imputation. So we did not specifically discussed those signals (in this example locus there are 2 haps with this variant in the ref panel) , but I do think

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@saorisakaue

Saori Sakaue

2 years

@martinjzhang @CMUCompBio Congrats Martin!!🙌👏🎉🎊

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@saorisakaue

Saori Sakaue

2 years

@TAmariuta Congrats Tiffany!!!🥰

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@saorisakaue

Saori Sakaue

3 years

@Eric_Fauman @masakanai it interesting! We might be able to see more evidence from WGS-based studies converging into this gene SLC5A5 in future👍

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@saorisakaue

Saori Sakaue

3 years

@Eric_Fauman @masakanai Thanks Eric for this interesting 🧵! We actually have reported this locus as novel but it is buried in Supplementary Table 4 line 130😀But yes we did not featured this loci in the manuscript and here is why👇

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@saorisakaue

Saori Sakaue

3 years

@emeKato Congrats!🎉

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Saori Sakaue

4 years

🎉Glad to be part of this tour de force study!

@GLettre

Guillaume Lettre

4 years

1/ The new paper by the Blood-Cell Consortium is now available at @CellPressNews . Exciting work by an incredible team: Chen, Raffield, Mousas, @nicolesoranzo , Johnson, Reiner, Auer and many more...

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@saorisakaue

Saori Sakaue

2 years

We present many interesting examples SCENT how is very useful in defining causal variant & genes in complex human diseases. E.g., tissue-specific causal variant & gene for female gynecological traits that was only found in SCENT from pituitary (hormone-secreting organ)!

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@saorisakaue

Saori Sakaue

4 years

@Eric_Fauman @masakanai @gem_epi @NanaMatoba Thanks, I am personally not confident if it is mediated solely by alcohol, considering the (assumed) biological pleiotropy of this locus.

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@saorisakaue

Saori Sakaue

2 years

We applied SCENT to all available #multiome data (including the new one from our group in rheumatoid arthritis patients) as of now, and identified 87,648 enhancer–gene links in total!

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@saorisakaue

Saori Sakaue

2 years

@Taichi_A_Suzuki Congrats👏👏🎉

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@saorisakaue

Saori Sakaue

4 years

@soumya_boston @harvardmed Thank you Soumya, I cannot thank you enough for making this happen (incl. immigration), and am so excited to work with you!!

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@saorisakaue

Saori Sakaue

5 years

We finally showed that even the subtle substructures had an unexpected and non-negligible impact on polygenic risk prediction. We are in a need for a practical methodology to derive PRSs to avoid the disadvantages of the underrepresented subpopulations. (4/5)

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@saorisakaue

Saori Sakaue

3 years

@FanZhang_Jessie @CUHealthAI @CUAnschutz How cool😍

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@saorisakaue

Saori Sakaue

5 years

@Eric_Fauman @okada_yukinori Thanks! I am looking forward to your talk too🙂

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@saorisakaue

Saori Sakaue

5 years

@FinnGen_FI We thank #FinnGen for this wonderful collaboration🙂

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