Co-led with the always awesome @mingxiangteng.bsky.social with data from the #ORIENNetwork #AsterInsights and @moffittnews.bsky.social. #clonalhematopoiesis #CHIPsm

qcCHIP: An R package to identify clonal hematopoiesis variants using cohort-specific data characteristics AbstractSummary. Clonal hematopoiesis (CH) is a molecular biomarker associated with various adverse outcomes in both healthy individuals and those with und

📢We developed a cool new R package to help determine optimal QC cutoffs for calling CHIP mutations based on your data!

qcCHIP: An R package to identify clonal hematopoiesis variants using cohort-specific data characteristics url: academic.oup.com/bioinformati...

Thank you, again, to my incredibly collaborative team. This project has been such a joy. Can't wait to continue to build on this story!

These results provide compelling evidence for the clinical significance of changes in CH allelic abundance (VAFs) during cancer treatment with implications across solid tumor types. We shed light on genes and muts that may be more prone to positive selection.

🚨 Finally, we show that, not CH in general, but **positive selection of CH muts** (eg, driven by chemo or radiation), is associated with OS, PFS, and RFS. These associations persist in multivariable, adjusted models.

These findings were corroborated in 2 external cohorts - one breast cancer and one pan-cancer cohort.

Neff was associated with dose - pts with higher exposure to chemo had smaller Neff (ie, stronger positive selection).

We defined a fitness likelihood for each mut and calculated the probability of its clonal expansion relative to the wildtype alleles. The highest fitness likelihood was under tx with chemo, where the fittest CH muts per pt were over 10,000x more likely to expand than wildtype.

Neff: the min. # of clonally independent alleles needed to explain the observed changes in VAF during tx in a pt.
Low Neff: strong / positive selection;
High Neff: weak / negative or no selection.
Chemo and chemo+rad exerted the strongest selective pressure on CH clones.

We adapted a method for estimating pathogen transmission population size to calculate the number of alleles that recapitulated the observed mutational dynamics during tx per pt - the effective allelic population size (Neff).

Long-term (up to 10 yr), CH VAFs continued to grow, with the largest increases in patients tx-ed with cytotoxic chemo.

The fitness landscape of CH is gene and mutation dependent. With chemo, TP53, YLPM1, PPM1D, and DNMT3A had the largest short-term changes in VAF. With breast radiation, ATM had the largest change in VAF. No effective changes in hormone tx only.

All post-tx CH muts were present before tx. All CHIP muts persisted at CHIP-defining VAFs; 4% of CH expanded to CHIP. Short-term, VAF changes were highest in pts tx-ed with chemo, followed by rad & chemo+rad; pts tx-ed with only hormone therapy had essentially no change in VAFs.

55% of patients had #CH before tx; 33% had #CHIP. Of those with CH, 56% had only 1 mutation (mut). We quantified clonal diversity using divergence in variant allele frequencies (VAFs) and show that as CH expands, a larger number of CH muts may arise, increasing clonal diversity.

We conducted ultra-deep error-corrected sequencing (>5000x) on serial samples from before, during, after, and long after treatment (tx) for breast cancer - with chemo, radiation, chemo+rad, or hormone therapy only - to measure CH changes over time.

#ClonalHematopoiesis / #CHIP is associated with worse survival in pts treated for solid cancers, but the evolutionary mechanisms driving differential CH dynamics are unknown. To get at this, we calculated therapeutic bottleneck sizes in pts treated for cancer.

📢 This has been a dream collaborative effort with an amazing group of investigators, notably @hkhiabanian.bsky.social, #MonaArabzadeh, #ShridarGanesan, #JeffreyWest, #SadeghMarzban, #StefaniaMorganti, @mingxiangteng.bsky.social, @jkresovich.bsky.social, @moffittnews.bsky.social, #NCI (funding)

Clonal Hematopoiesis Dynamics and Evolutionary Fitness During Cancer Treatment Impact Clinical Outcomes Clonal hematopoiesis (CH) is the age-related expansion of mutated hematopoietic stem cells without other hematologic abnormalities. In patients with solid tumors, CH is associated with higher mortalit...

🚨📢❗So proud and excited to share our latest work, "Clonal Hematopoiesis Dynamics and Evolutionary Fitness During Cancer Treatment Impact Clinical Outcomes", now available: www.medrxiv.org/content/10.1...

Metformin reduces the competitive advantage of Dnmt3aR878H HSPCs - Nature Dnmt3a mutations in mouse haematopoietic stem and progenitor cells equivalent to R882 mutations in human cause increased mitochondrial respiration, suggesting that this is a mechanism of clonal h...

www.nature.com/articles/s41...

Linking identified variants to tumor sequencing (n > 390k patients), we show that pathogenic CH (#CHIP) mutations are commonly detected across tumor types and associated with 𝘺𝘰𝘶𝘯𝘨𝘦𝘳 age in patients with solid tumors suggesting differential biology.

We identified differences in SM and CH rates and mutations across genetic ancestry groups. We provide a catalogue of identified variants.

We used allele-balance and age skewing to identify SM and CH mutations in population-level data.

Peripheral blood somatic mosaicism and clonal hematopoiesis across ancestry backgrounds Somatic mosaicism (SM), the presence of somatic mutations, is classified as clonal hematopoiesis (CH) when it occurs in hematopoietic cells at an age-related rate. CH is associated with risk for hemat...

🚨🚨 Our new manuscript is now available online!
Co-led with the awesome @mingxiangteng.bsky.social and not possible without our amazing team. 🧪🧬

www.medrxiv.org/content/10.1...

Well this is cool!! 😎

How ‘bout the make-up study sections next?!!

Friendly reminder: if you are waiting on something from a US-based scientist/reviewer/editor, please realize that we're barely making it through each day putting out non-stop fires and trying not to collapse into tears. We're trying our best, but things will take longer right now. Give grace.

So good! Me, 2014.

As we can expect PubMed dysfunction more and more or to be swamped with fake journals I suggest you get acquainted to this nice alternative: europepmc.org

ASPR COVID-19 Testing NAVIGATION

#MedSky #IDSky #PublicHealth
If you haven’t ordered your free #COVID19 home rapid tests recently, every US household is eligible for four more at no cost, incl shipping. It takes under a minute & does not require a credit card. Order ASAP…Pls repost to spread the word.

Go to Covidtests.gov.

NIH In Your State - United For Medical Research Select a state on the map to see the impact of NIH funding across America.

In Florida:

NIH Awards Funding:
$914 M

Jobs Supported:
14,688❗️

Economic Activity Supported:
$2.78 B❗️

www.unitedformedicalresearch.org/nih-in-your-...