Functional human genomics @ KTH, SciLifeLab, NY Genome Center. Pro science here, more fun stuff fun at
@tuuliel
. Mastodon tuuliel_lab
@genomic
.social
Very happy and proud to present: The GTEx papers. This set of 15 papers published today describes the final phase of this 10-year effort, providing the genomics community an atlas of genetic regulatory variants and a deep dive into the biology behind it.
Excited to share the news: I will be moving to Sweden in May to start as a Professor of Genomics at Royal Institute of Technology, and as the Director of National Genomics Institute at
@scilifelab
. I'll continue to run a lab at
@nygenome
as an Associate Faculty Member.
Excited to share our paper, out today in
@Nature
, where we characterize transcriptome variation in human tissues by long-read sequencing. Huge thanks to
@g_dafni
@beryl_bbc
Garrett Garborcauskas
@dgmacarthur
and other collaborators. 🧵
Interested in doing a PhD with me in Sweden? Experimental+computational genomics skills or interests? We have an open position! Great environment at KTH on
@SciLifeLab
campus, staff benefits, well-funded project, close interactions with our New York team. Link in the replies 👇
We know the importance of subtle gene dosage variation, and yet the main tool of molbio is gene KO/KD. In our new preprint,
@JuliaDiumenge
introduced subtle modulations of transcription factor dosage by CRISPRi/a, and quantified responses by scRNA-seq. 1/
I have been informed that I am being replaced as the Editor in Chief of
@eLife
for retweeting a
@TheOnion
piece that calls out indifference to the lives of Palestinian civilians.
Excited to share our review paper in Cell! With
@SashaGusevPosts
@s_ramach
@yang_i_li
we discuss the genetic and molecular architecture of human traits, future opportunities and challenges and ways forward.
We’re recruiting for multiple positions in my lab in New York and Stockholm, at MSc and PhD levels. If you’re interested in pursuing creative systems genetics questions with tools/data like Developmental GTEx, CRISPR and single-cell, please read further / share. 1/
The Leena Peltonen Prize of 2024 goes to
@SashaGusevPosts
🎉! I was honored to announce this and introduce Sasha just minutes ago at
#ESHG24
. Huge congrats!
As scientists, we all try create new knowledge & methods. Many of us approach this with a positive attitude of "happy to present our contribution, hoping you find it useful". For some, the focus is on berating other people's work and lifting their own by pushing others down.
#sad
Proud to present our molecular QTL primer! All you've ever wanted to know about mapping genetic associations to molecular traits. We discuss data, methods, interpretation, and opportunities and challenges in the field.
A real moonshot project in biomedical research would be a decisive legal, regulatory and IT effort to really make data access work for researchers across the world. Less sexy, but better bang for the buck & more transformative than e.g. AI, CRISPR, ginormous sequencing projects.
This is huge. And while TOPMed was the first project with massive-scale WGS - and should be praised for the higher diversity of ancestries - the impact of UKBB is likely to be way higher due to less red tape in accessing the data.
#UKBiobank
has made the
#WholeGenomeSequencing
data of 200k participants available to approved researchers. These data will help researchers understand the genetic determinants of disease and may accelerate innovative drug discovery work. More info here:
Excited to share our latest paper, using CRISPR and single cell sequencing to characterize GWAS locus effects on gene expression in cis and trans. Huge thanks to
@johnomix
,
@nevillesanjana
and other collaborators!
🚨Our work on multi-modal, single-cell pooled CRISPR screens to study GWAS variant-to-function, STING-seq, is now out in
@ScienceMagazine
! Read on for 6⃣ of the main findings from our study, led by myself and co-advised by
@nevillesanjana
and
@tuuliel
! 🎉
Happy and honored to receive the Göran Gustafsson prize in molecular biology! It's always inspiring to see our work recognized. Special thanks to current and former lab members and collaborators for making this possible.
Five years ago I switched from buggy Endnote to Papers to manage references, and now Papers has become just as bad. What next? Any recommendations? Compatibility with Google Docs would be a major plus now that many papers/grants are written there.
A new preprint from the lab, with
@mollymozzarella
@stephanecastel
and others! We developed methods for RNA-seq from non-invasive biospecimens. TL;DR: hair follicles and urine have major potential for large-scale transcriptomics. 🧵👇
Excited to share a new preprint from my lab, led by
@silvakasela
✨, analyzing cellular and environmental modifiers of regulatory variants in the TOPMed multi-omics pilot data from the MESA cohort. 🧵
Ten years ago I started my lab. What a time it's been - working with great people (👇 & more 🙏), exciting science, interesting times.
I still don't quite understand how I've been so lucky. I got everything that I ever wanted and probably more than I dared to dream of.
We're looking for a new faculty colleague at the New York Genome Center! We welcome applications in all areas of human genetics or genomics. Please feel free to reach out to me or other faculty to chat; applications by April 1:
We're hiring!
@david_a_knowles
and I at
@nygenome
are looking for a jointly mentored postdoc to work on functional genomics and/or statistical genetics. We offer top notch data, great environment & a fun city! Happy to chat informally, please RT.
We're recruiting postdocs! Join our lab at
@scilifelab
@KTHuniversity
in Stockholm to work on functional genomics at the experimental and/or computational intersection of CRISPR/scRNA-seq/genetics approaches. Close links to our team at
@nygenome
. 1/
I'm hiring staff & postdocs for my Stockholm lab! Cool projects in experimental/computational functional population genomics, cutting-edge environment at
@scilifelab
@KTHuniversity
in lovely Stockholm, close interactions with my lab at
@nygenome
. Please RT
Beautiful preprint from
@jkpritch
and Alex Marson labs. The insights from CRISPR + single cell have huge potential in uncovering regulatory networks underlying functional genetic architecture of human traits. This type of data will be transformative.
Looking for suggestions for modern textbooks in areas that my diverse lab covers - to help lab members quickly build a foundation in an area where they have less background. Popgen, human genetics, func genomics, molbio, modern biostats & bio data science... Help!
We're looking for a postdoc in Stockholm! Co-mentored position at the intersection of biology/genomics and ML. Fantastic environment at
@KTHuniversity
&
@scilifelab
's Data Driven Life Science community, with strong international networks. Please RT!
Six weeks left until the abstract deadline for Biology of Genomes at CSHL
#BoG24
! We have a stellar lineup of keynotes and discussion leaders (=~invited speakers), and look forward to another brilliant meeting in May 7-11. Abstract submission & info:
John Morris
@johnomix
, postdoc with me &
@nevillesanjana
at
@nygenome
at
#bog22
: Systematic targeting and inhibiting of noncoding GWAS loci with single-cell sequencing. This is an update (with lots of new data & insights) of our preprint.
My department at
@KTHuniversity
@scilifelab
is recruiting an Assistant Professor in computational biology! Fantastic academic environment, top notch infra, colleagues and students, international vibe, Sweden is a lovely place to live. More info 👇
Open postdoc position in my lab! Functional genetic variation with computational or experimental focus, cutting-edge data & tech, fantastic environment in Stockholm at
@scilifelab
, interactions & opportunity to spend time in the New York lab. Please RT!
One week left to apply for junior faculty positions in the Data Driven Life Science program in Sweden! Competitive startup, big program with a strong peer+mentorship networks, great country with strong science, international vibe and nice quality of life.
I've been coming to
#bog24
since 2007 (I think), and I see many other veterans and old friends at Grace now. One of the best things about this meeting is all the new faces. Here's my protips for the meeting:
New preprint 🎉 led by
@AervaI
👇! We introduce an approach to prioritize biological driver genes by recalibrating differential expression fold changes with population variance. This extracts new meaning out of DE analysis, which is a cornerstone of computational biology!
Folks at
#BoG23
and others - I'm recruiting postdocs to my Stockholm and New York teams. Reach out if interested - experimental or computational opportunities in gene expression dosage (talk
#39
), GWAS+CRISPR+molQTLs, developmental GTEx, etc.
I asked ChatGPT to write me a "no thanks" email to requests for my time and people are responding to it so much better than when I wrote it myself. That machine is better at emotional labour than I am (maybe it's the repetition)? The text in question:
Hello world! It's Tuuli. This is my new strictly science account for the genetics/genomics community 🤓. You'll find
#scicomm
, policy, life, etc. tweets for a more general audience at
@tuuliel
😎. I'll cross-tweet sometimes.
We introduce the largest long-read transcriptome sequencing data from human tissues from
@gtexportal
. The
@nanopore
technology provided an opportunity for improved analysis of the real biological units of the transcriptome: transcripts - not just genes or splice junctions. 2/7
Thrilled to receive the ERC Consolidator grant - the first big external grant for my rapidly growing Swedish lab! We'll be digging deep into variation in gene expression dosage and its role in genetic architecture of human diseases. 🎉🥳
KTH-forskarna Madeleine Balaam, Ricardo Vinuesa, Tuuli Lappalainen och Lisa Prahl Wittberg får omkring två miljoner euro vardera i ERC Consolidator Grants från Europeiska Forskningsrådet.
Xiaoting Li from the Bussemaker lab at Columbia presenting our collaborative project: Identifying genetic regulatory variants that affect transcription factor activity. New method for estimating TF activity from expression data applied to GTEx for GWAS mapping
#BoG22
I'm excited to share our new preprint, led by my postdoc
@g_dafni
and
@beryl_bbc
in collaboration with Garrett Garborcauskas,
@dgmacarthur
,
@nanopore
and others: Transcriptome variation in human tissues revealed by long-read sequencing.
Thread here:
I'm excited to share our new preprint, led by my postdoc
@g_dafni
and
@beryl_bbc
in collaboration with Garrett Garborcauskas,
@dgmacarthur
,
@nanopore
and others: Transcriptome variation in human tissues revealed by long-read sequencing.
Thread 👇
The truly sweet part of the move for us is getting closer to family who live in Finland and Sweden. It’s been an awesome adventure of 12 years since I finished my PhD and left Finland; 7 years in NYC. But now it’s time to go home to Scandinavia - next chapter of the adventure.
There is also a large number of companion papers from the consortium that dig deeper into specific questions and introduce novel data sets and methods. Full list here, and keep an eye on updates as additional papers get published.
Interested in engaging in research using data-driven approaches? The SciLifeLab and Wallenberg National Program for Data-Driven Life Science (
#DDLS
) is now recruiting 19 new high-profile young researchers as DDLS Fellows.
@KAWstiftelsen
#SciLifeLab
A new preprint from the lab! We dug into transcription factors as drivers of eQTL activity and its variation across individuals and tissues, using GTEx and other data sets. Led by the brilliant
@EliseScience
whose thread summarizes the approach and the findings 👇
#bog22
here we gooooo! Awesome to be back and see old friends and new faces. Fighting my jetlag but excited about the functional genomics session (including the talk by our very own
@johnomix
!)
We identified about 100K novel transcripts that typically validate well in proteome MS data. They're enriched for tissue-specific expression - maybe that's why they were missed before. We see a lot of potential for transcript annotation in humans and other organisms. 3/7
Great to see this paper published!
@xiaoting_l
and
@HarmenBussemkr
developed a really creative way to robustly quantify TF activity, which we then used as a phenotype in GWAS.
Excited to share that our paper came out in Cell Genomics last week. We developed a model to estimate TF regulatory activity from GTEx RNA-seq data and mapped genetic variants (“aQTLs”) predictive of this virtual trait.
FYI to those unfamiliar with the Swedish system, PhD students take courses alongside their research projects, but you apply directly to a lab instead of a program. These are employed positions with benefits - no need to put your life on hold for 4 years to pursue a PhD!
A new preprint from the lab, with
@mollymozzarella
@stephanecastel
and others! We developed methods for RNA-seq from non-invasive biospecimens. TL;DR: hair follicles and urine have major potential for large-scale transcriptomics. 🧵👇
@nomad421
@GarmireGroup
This. Also, this is a way for everyone to know what their lab mates are actually working on - otherwise is it a team or just a bunch of individuals sitting in the same office?
Join us at SciLifeLab & KTH! Great environment, heavy investment in computational biology, tons of data being produced, international atmosphere. Sweden also has a great culture for work/life balance. A couple of weeks left to apply.
Recruiting SciLifeLab Fellow (Assistant Professor) in
#MachineLearning
in Computational Biology, employed by
@KTHuniversity
The position comes with generous financial support for recruiting a team and sustaining research activities
Learn more and apply↓
Excited to share a new preprint from my lab, led by
@silvakasela
✨, analyzing cellular and environmental modifiers of regulatory variants in the TOPMed multi-omics pilot data from the MESA cohort. 🧵
Congrats to
@ngisweden
,
@NBISwe
,
@BioMS_Sweden
, NMI (National Microscopy Infrastructure), Ancient DNA (
@SciLifeLab_ADF
(Part of Archlab)) and everyone else who has been awarded grants within the call Research infrastructure of national interest! 🌟
In the main paper, co-led with
@francoisaguet
and
@KArdlie
, we introduce the data set of eQTLs and sQTLs in cis and trans from >15K samples from 49 tissues, analyze functional mechanisms, tissue- and cell-type specificity, GWAS interpretation, and more.
@shyam_lab
@anshulkundaje
I have the exact same if not higher standards for our preprints - I'd endanger my professional reputation in the eyes of the entire community (not just a few ppl) if I posted utter crap. And that reputation, rather than papers, is the real currency that makes or breaks careers.
New preprint from our lab! We dug deeper into interpretable splicing changes linked to common genetics variants, including predicted changes in protein structure w
#alphafold2
. Huge thanks to
@EinsonJ
for driving this this project and writing the thread 👇 !
Excited to announce that my paper entitled "The impact of genetically controlled splicing on exon inclusion and protein structure" is finally out on bioRxiv!
#bioRxiv
#biorxiv_genomic
3 days left to apply for our postdoc position in Stockholm! Co-mentored project at the intersection of genomics and ML. Fantastic environment at
@KTHuniversity
&
@scilifelab
's Data Driven Life Science community, with strong international networks.
We're looking for a postdoc! Cool ERC-funded project digging into gene dosage variation with CRISPR+sc+computational methods. Dynamic environment at KTH / SciLifeLab Stockholm campus, plus interactions with our New York team. Apply or email for more info:
Exciting news! My first paper, "Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs," is now out on bioRxiv! Check it out:
#biorxiv_bioinfo
1/5 🧵
We detected transcriptional effects of dosage modulation of 3 TFs. Nonlinear responses are common and distinct for up/downregulation - which makes biological sense, but highlights the difficulty of capturing this without gradual dosage modulation. 3/
@AdamRutherford
I had an argument about this with a very high-ranking genetics professor 10 years ago - he thought that the probabilistic perspective is just intellectual laziness and all genetics worth studying is deterministic. 🤯😂
Excited to share a new preprint from the lab! We dug into splicing QTLs as modifiers of penetrance of rare deleterious variants in their target exons, using data from GTEx, TOPMed, SSC. See thread from
@EinsonJ
(and the preprint!) for more details 👇
Anyone? We've done some work looking at expression level vs eQTL effect size across tissues for GWAS loci (see GTEx 2020. TL;DR it's complicated). We didn't look specifically for these situations though; my gut feeling is that it's rare.
@khmiga
@EichlerEE
The next article in the series comes from
@tuuliel_lab
@ee_reh_neh
& colleagues
📰Increasing diversity of functional genetics studies to advance biological discovery and human health
@Eric_Fauman
@pfizer
Very nice! And astonishingly good agreement with analysis we did for eQTLs in the GTEx main paper of 2017 (using allele-specific signal to separate cis/trans). The good old 1 Mb threshold for cis effects is 💎
There seems to be a method to the madness. For me, moving/setting up a lab has been like: -6mo: the thrill of a twitter announcement, -3-0mo: moving stress and admin confusion, 0-3mo: total chaos and lots of excitement, 3-6mo: vague understanding of how things work.
Week 2: So thrilled our piece, “The transition phase: preparing to launch a laboratory” is out in
@TrendsBiochem
! We created this resource to guide incoming group leaders. Thank you to my dream team collaborators
@karalmckinley
@DrDidychuk
@QuinaScience
@nilshomer
Not sure if I can call myself a bioinformatician but: Start from simple analyses/methods - you'll learn about the data, which will help you to pursue more ambitious approaches. And quite often you'll find that simple approaches - when used with care - are sufficient.
I have work email & Slack on my phone, but notifications turned off. No email notifications on laptop either, and only selectively for Slack.
Also, I've taught myself to feel no guilt when I've chosen not to work. When I'm out, I'm out.
I am making a list of new boundaries to change my life.
The first will start next week: I am taking my work email off my cell phone.
Faculty folx who’ve done the workplace unravel but are still faculty, what else do you recommend? Other folx?
We were able to gradually up-and downregulate gene expression by sgRNA tiling around TSS in K562 cells with either CRISPRa or CRISPRi. Readout with ECCITE-seq with targeted scRNA-seq for high-quality quantifications. This is a scalable approach that is easy to apply. 2/
Finally, we demonstrate potential in better interpretation of rare variants, both by improved transcript annotation and by describing how rare variants disrupting transcript structure manifest in long-read transcriptome data. 6/7
To analyze genetic effects by allele-specific expression and transcript structure analysis, we first developed a new tool, LORALS, to extract these data from long reads in a scalable manner, accounting for specific properties of these data. LORALS is available in github. 4/7
Summary data are available in , and the sequencing data are available via GTEx protected access. I hope to see many further uses for these data and also the technology - lots of potential for further discovery and applications! 7/7
I’m thrilled to join one of the strongest biomedical hubs in Europe, continue my research at
@KTHresearch
with new collaborations, and contribute to the fantastic technology hub that
@scilifelab
is. I’ll be recruiting staff, postdocs and students to my new lab - stay tuned!
After many struggles with the sparsity of allelic series in genetic insights to the dosage-to-function question, I'm very excited about our new molecular biology approach to this question. This is just a pilot study, and we're continuing this line of work in the lab. 6/6
🎉 Exciting update on our work with the eQTL Catalogue! We're diving deep into understanding genetic variants associated with complex traits in non-coding regions of the genome.
@vagar112
IDK. If graduate student or a postdoc works their ass off for years to produce a data set, and then someone who’s quicker at analysis publishes the key discoveries the trainee has been dreaming to pursue…even if they get a data set citation and credit, is that a great outcome?
It is with great sadness that we share the news that Dr. Casey Brown passed away on Saturday, March 18. He was a friend, colleague, and mentor to so many in the GCB and CAMB communities, as well as the scientific community as a whole, and will be deeply missed.
It is a major challenge to fine-map causal variants within genetic associations due to linkage, so a common assumption is that a single variant drives a given signal. But how many variants could really be causal? Check out our new paper from
@sbmontgom
lab
Now in eLife! Single-cell RNA-seq led to a surprising model of alternative splicing: individual cells make one isoform or the other, but rarely both in one cell. Carlos Buen Abad Najar, with Nir Yosef and me, shows this is an artifact of low mRNA recovery.
The bittersweet part is leaving Columbia and transitioning from a Core to Associate Faculty at NYGC. It’s been amazing, with great research environment & colleagues, but all good things come to an end. But I’ll still have a lab at NYGC and I’ll be around in NYC quite a lot!