iiinova — where your digital self keeps evolving

Nicolas Alcala @nalcala.bsky.social · 27/08/2026

This study has been years in the making! Thanks to all the people involved in the study🙏 Especially Alexandra Sexton-Oates, Emilie Mathian, @matthieufoll.bsky.social and Lynnette Fernandez-Cuesta, but also all the other authors, the cancer centers involved, funders, and patients!

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

Overall, summarizing all this info, we feel that it is time for the #NET community to embrace this molecular classification and integrate it with the current grade classification. There are so many biological differences among molecular groups that this will definitely be critical for patients

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

On the diagnosis front, we used #AI (ViT) and a great team of pathologists to find morphological features associated with each group. AI is actually much better at recognizing molecular groups than recognizing current entities from the WHO classification!

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

... this matches #spatialtranscriptomics patterns: supra-carcinoids actually tend to have restricted supra-carcinoid regions forming ecological niches with fibroblasts and macrophages, coexisting with regions from another group. Supra-carcinoids thus probably evolve from other groups

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

Molecular groups are very stable: if you sequence two regions from a same tumor they will be very similar. This suggests that they were indeed different diseases from the start... except for supra-carcinoids: one region can be much more supra-carcinoid than the other...

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

We also investigated #selection (dn/ds) in neoantigen rich regions. We find negative selection in supra-carcinoids, suggesting that the immune system did its job in the past but got overwhelmed. And positive selection in the B group among smokers, suggesting that smoking might promote some NETs!

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

...and driver #mutations also increase with grade within each group, suggesting that having multiple drivers either predisposes to more aggressive #tumors, or that accumulation of drivers drives aggressiveness 🤔

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

Nevertheless, we found that the number of mutations increased with grade within each group...

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

For the #cancer #evolution crowd here, we used multi-regional (and also the other) samples to reconstruct basic phylogenies and found.... very simple trajectories: a single genomic event is usually enough to lead to lung #NETs

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

These #tumors also do not happen in the same patients, and not in the same location in the lungs, suggesting potentially different causes. One group may be more associated with #smoking (B) while another is frequent in younger women (A2)

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

Sequencing ~100 samples with #WGS, we find that the four molecular groups do not have the same #genomic causes: group A1 mostly harbour small and structural variants while A2 and B have amplifications, and supra-carcinoids have a lot of everything

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

Actually, lung NET molecular groups better explain molecular differences between patients than any official classifications of lung cancers 🤯

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Nicolas Alcala @nalcala.bsky.social · 27/08/2026

Lung NETs split very strikingly into four molecular groups, which is something that we don't observe in NETs from other organs, or even between small- (SCLC) and large-cell neuroendocrine carcinomas (LCNEC), although they are recognized as separate entities

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Reposted by Nicolas Alcala

Alison Feder @alisonfeder.bsky.social · 10/09/2025

Sam Hart describes and applies a method to distinguish differences in mutational processes between groups of cancers without signature decomposition (joint work with @kelleyharris.bsky.social and in collaboration with @nalcala.bsky.social )! #Genomics 🖥️ 🧬 www.biorxiv.org/content/10.1...

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Reposted by Nicolas Alcala

Jeffrey Ross-Ibarra @jrossibarra.bsky.social · 09/04/2025

Regular ask to send me successful job applications, grants, and fellowships to share with others! Thanks to @isabelott.bsky.social for sharing her GRFP (and congrats!). github.com/RILAB/statem...

github.com

GitHub - RILAB/statements: Successful Job Applications and Grants

Successful Job Applications and Grants. Contribute to RILAB/statements development by creating an account on GitHub.

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Reposted by Nicolas Alcala

Maike Morrison @maikemorrison.bsky.social · 14/03/2025

1/ Hey y'all, I'm excited to share my latest paper, which is out now in PNAS! We introduce FAVA, a statistical framework to measure compositional variability across microbiome samples. If you want to measure variability across a stacked bar plot, FAVA is for you! Paper: doi.org/10.1073/pnas...

5 relative abundance plots arranged to have increasing compositional variability (variability across relative abundance samples, here vertical bars)

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Nicolas Alcala @nalcala.bsky.social · 31/01/2025

Inspiring talk from @matthieufoll.bsky.social and Lynnette Fernandez-Cuesta about the future of #lung #neuroendocrine #tumor classification and clinical management, and how to use #AI to learn simple morphological features to recognize molecular subtypes #CRCL25

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Nicolas Alcala @nalcala.bsky.social · 29/01/2025

@lisemangiante.bsky.social from @stanfordpress.bsky.social : breast #cancer adopt specific ecological strategies to adapt to their microenvironment 🤯 #CRCL25

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Reposted by Nicolas Alcala

Sandra Ortiz-Cuaran @sandraortizcuaran.bsky.social · 29/01/2025

Impressive talk by Lise Mangiante on tissue ecology from ER+ breast cancer. #CRCL25 www.nature.com/articles/s41...

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Nicolas Alcala @nalcala.bsky.social · 29/01/2025

How do lung #neuroendocrine #tumors and their microenvironment coevolve ? Great talk by Alexandra Sexton Oates at #CRCL25 #LungNETs #lungcancer

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Reposted by Nicolas Alcala

Sandra Ortiz-Cuaran @sandraortizcuaran.bsky.social · 29/01/2025

Great kick-off of the #CRCL25 symposium with a keynote lecture by Joan Massague, on metastasis initiation. www.crclsymposium2025.fr/en/program/d...

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Reposted by Nicolas Alcala

SMTPB @smtpb.bsky.social · 03/12/2024

Members, check your inboxes for registration links for the upcoming Wikipedia Edit-A-Thon, hosted by @joannamasel.bsky.social! December 5th at 9:00 AM PT.

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