Barbara Hernando

Barbara Hernando

@bhernando.bsky.social

Postdoctoral Junior Leader at CNIO funded by LaCaixa | Cancer genomics, evolution & early detection | Heptathlete forever

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Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
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Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

15/ Two more: non-canonical impaired HR was enriched in patients of African ancestry, and late-onset disease was dominated by replication stress while early-onset was enriched for HRD. Age at onset and aetiology are linked.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

13/ Notably, the same Cox models on individual signatures, one class at a time, showed no strong risk associations in this cohort. The prognostic signal lives in the integration, not in any single class.

Barbara Hernando
@bhernando.bsky.social

14/ Extending to mCRPC (HMF, n=240) we emulated an RCT: IMF6-high patients had markedly lower risk of treatment failure on ARPIs vs taxanes (HR 0.21). Retrospective, n=25 vs 94, hypothesis-generating – but mechanistically coherent via SPOP.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

11/ Prevalence, in CIN tumours: AR-mediated mutagenesis dominant in 39%, replication stress 28%, ROS 21%. Replication stress being this pervasive in treatment-naive primary disease was not expected in a cancer we call slow.

Barbara Hernando
@bhernando.bsky.social

12/ Clinical: 4 IMFs (ROS, AR, non-canonical HR, canonical HR) carried HRs of 4–7 for metastasis vs non-CIN, independent of age, Gleason grade group, stage, TMB and late-to-early RT ratio. And they stratified WITHIN GG2/GG3 – the actual grey zone.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

9/ The eight: MMRd; ROS-mediated mutagenesis; AR-mediated mutagenesis; mitotic defects + replication stress; non-canonical impaired HR; replication stress; APOBEC; canonical impaired HR.

Barbara Hernando
@bhernando.bsky.social

10/ Topography mattered. SNVs and SVs are enriched at tumour-specific ARBS — and SBS1 is DEPLETED there. Why? AR binds unmethylated CpGs. We confirmed it directly with Nanopore methylation in 8 tumours.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

7/ Result: 8 integrated mutational footprints (IMFs). Important: these are NOT subtypes. Every tumour carries activities across several IMFs; what differs between patients is which processes are running and how strongly. A spectrum, not eight boxes.

Barbara Hernando
@bhernando.bsky.social

8/ Challenge 3: every cluster had to earn its aetiology. Orthogonal evidence: driver status across 1,747 curated genes, DDR pathway deficiency, HRDetect, MSIsensor-pro, replication timing, hypoxia and AR pathway scores from RNA. Then replication in TCGA-PRAD.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

6/ Challenge 2: the four alteration classes aren't on a common scale, and mutational processes nest. Solution: normalise activities, then hierarchical clustering – swept parameters, arbitrated on stability, silhouette AND known biology.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
View full thread
Barbara Hernando
@bhernando.bsky.social

3/ Substrate: 959 primary tumours from 1,001 PPCG donors, 7 countries, uniformly reprocessed, germline + somatic called the same way, median 7 yrs clinical follow-up. 4.7M SNVs, 292K indels, 74K SVs, 55K CNAs.

Barbara Hernando
@bhernando.bsky.social

4/ Challenge 1: the SV description was too coarse for prostate cancer. Solution: extend it. We classified each rearrangement by class × size × replication timing × fragile site – and, new here, by whether it fell at an AR binding site (ARBS). 6 stable cSV signatures came out.

Barbara Hernando
@bhernando.bsky.social

1/ NEW PAPER 🎉 🧵 We mapped the mutational processes shaping 959 prostate cancer genomes from the Pan Prostate Cancer Group (PPCG), integrating SBS, ID, CX and complex SV signatures. Eight footprints account for the processes in 85% of cases www.nature.com/articles/s41... @nature.com

nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
Barbara Hernando
@bhernando.bsky.social

2/ Motivation: signature analysis has been siloed by variant class. But one broken mechanism doesn't confine itself to one class — the same failing machinery that miscopies a base also duplicates a segment and shatters a chromosome. Read them separately, see four things.

Barbara Hernando reposted

Joachim Weischenfeldt
@jweischenfeldt.bsky.social

Read our cool study out in @nature.com 🧬 great work by Andreas Gruber, André Vidas Olsen, @bhernando.bsky.social and Kevin Cheng. Co-led with @reimand.bsky.social and @gmaci.bsky.social Read post here: tinyurl.com/3abceaev Also great media coverage here: tinyurl.com/yz8mcb98

linkedin.comVery excited to see our study online today in Nature!!! Amazing tour de force collaborative effort and fantastic collaborators within the Pan Prostate Cancer Group (PPCG) 🥂 Biotech Research &… | J...Very excited to see our study online today in Nature!!! Amazing tour de force collaborative effort and fantastic collaborators within the Pan Prostate Cancer Group (PPCG) 🥂 Biotech Research & Innovati...
Nature@nature.com

Nature research paper: Integrated signatures define mutational processes in prostate cancer go.nature.com/4xLwBNN

go.nature.comIntegrated signatures define mutational processes in prostate cancer - NatureEight integrated mutational footprints collectively explain the mutational processes in 85% of primary prostate cancer genomes.
Barbara Hernando
@bhernando.bsky.social

Check it now! 💫 Exited to share this preprint, the result of a fantastic collaboration between Sarah Aitken’s and Martin Taylor’s labs. During my secondment at @yalecancer.bsky.social @yalepathology.bsky.social, I contributed to explore how H&E images can be used to predict tumour genomics

Sarah Aitken@s-j-aitken.bsky.social

🔬NEW PREPRINT🔬 Explainable machine learning relates histological to genomic pathology www.biorxiv.org/content/10.6... From John Connelly and Barbara Hernando @bhernando.bsky.social, co-led with Martin Taylor @mstaylor.bsky.social - along with others from #LCEConsortium #genomicPathology #ml #ai

Barbara Hernando reposted

Sarah Aitken
@s-j-aitken.bsky.social

🧬NEW PAPER🧬 To what extent is cancer development deterministic? Does the germline genome affect that predictability? Find out in our #StrainDifferences paper @nature.com "Genetic background sets the trajectory of experimental cancer evolution" www.nature.com/articles/s41... 🧵[1/14]

nature.comGenetic background sets the trajectory of experimental cancer evolution - NatureExperimentally replaying tumour evolution in divergent mouse strains reveals the importance of interactions between genetic ancestry and acquired cancer-driving mutations in shaping the earliest stage...
Barbara Hernando
@bhernando.bsky.social

Thanks for everything! I will miss being around in the lab but see you online 🫶🏻

Sarah Aitken@s-j-aitken.bsky.social

It has been an absolute pleasure to host @bhernando.bsky.social here at @yalecancer.bsky.social for the last few months! I've learnt so much, and your generosity and enthusiasm will be greatly missed. Looking forward to future collaboration, friendship - and paella 🤩 @yalepathology.bsky.social

Barbara Hernando
@bhernando.bsky.social

Had a lovely dinner today with members of @s-j-aitken.bsky.social’s lab to celebrate my recent preprint! Sharing these small milestones (and the joy that comes with them) with friends is just magic ✨

Barbara Hernando@bhernando.bsky.social

📢 New preprint out! We are thrilled to introduce our framework to track #ongoingCIN by leveraging single-cell genomics and CIN signatures: www.biorxiv.org/content/10.1...

biorxiv.orgTracking ongoing chromosomal instability using single-cell whole-genome sequencingChromosomal instability (CIN) generates aneuploid genomes that are characteristic of most cancers. While bulk genome sequencing reveals historical CIN, it lacks the resolution to identify ongoing CIN ...
Barbara Hernando
@bhernando.bsky.social

It was an honor to take part in the @yalepathology.bsky.social research retreat today! Great science, inspiring discussions, a fun “guess who?”, and wonderful people. Huge thanks to organizers for such a great work! Can’t believe only 2 months left to enjoy this amazing #AitkenLab team ✨

Sarah Aitken@s-j-aitken.bsky.social

Today was our first Yale Pathology Department retreat - with Klaske, Barbara, Jacob, and Vanessa (we missed you Tanuja!) Great to present our work with a poster and two talks, share ideas, and meet new people 🇨🇦🇪🇸🇬🇧🇳🇱🇺🇸🌎 @yalepathology.bsky.social @bhernando.bsky.social

Barbara Hernando
@bhernando.bsky.social

Exciting 3 months ahead at the #AitkenLab @yaleschoolofmed.bsky.social! 🤩 Huge thanks to @s-j-aitken.bsky.social for the warm welcome, and to @caixaresearch.bsky.social for supporting my research career at all levels ✨

Sarah Aitken@s-j-aitken.bsky.social

🥳 Today we welcome Dr Bárbara Hernando @bhernando.bsky.social to the #AitkenLab @yaleschoolofmed.bsky.social Bárbara joins us from #CNIO as part of her @caixaresearch.bsky.social Postdoctoral Junior Leader Fellowship @yalepathology.bsky.social @yalecancer.bsky.social @cniostopcancer.bsky.social

Barbara Hernando
@bhernando.bsky.social

💥New preprint from the @gmaci.bsky.social lab! Thrilled to share this major team effort, with #Angel as co-first author, now live on bioRxiv! Check out our threat to learn more about our work👇

Geoff Macintyre@gmaci.bsky.social

If tumour genome evolution is deterministic, can we forecast genomic changes? Yes we can! At least for oncogene amps and tumour suppressor dels. @bhernando.bsky.social Angel Fernandez-Sanroman present our method for forecasting driver gene copy number change. Preprint: bit.ly/4kxF14y ⬇️1/

bit.lyForecasting oncogene amplification and tumour suppressor deletionOncogene amplification and tumour suppressor deletion can drive tumour initiation, progression and treatment resistance. Detection at diagnosis often signals poor prognosis, but it can also enable opp...
Barbara Hernando
@bhernando.bsky.social

Day 1 at #AACR2025 from my side! Meanwhile, at the #EMBO workshop on Chromosome Segregation and Aneuploidy, Maria Escobar will be presenting our project on ongoing CIN in KRAS mutant pancreatic organoids! A must meeting for the #CIN community meetings.embo.org/event/25-ane...

meetings.embo.orgChromosome Segregation and AneuploidyAneuploidy is a hallmark of cancer and developmental disorders such as Down syndrome. Understanding how cells accomplish faithful chromosome segregation and how chromosomal instability (CIN) impacts …

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