John Greally

Identification of de novo variants from parent-proband duos via long-read sequencing While de novo variants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available,...

Looks like @leandrosboukas.bsky.social has been busy doing useful stuff. DNV detection in duos, very valuable in communities in which families are less stable.

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

You’re the first person I know to have received the book!

Epigenetics: History, Molecules, and Diseases Buy Epigenetics: History, Molecules, and Diseases on Amazon.com ✓ FREE SHIPPING on qualified orders

My book on Epigenetics: History, Molecules and Diseases

www.amazon.com/Epigenetics-...

#EpigeneticsBook #Epigenetics

I'm more worried that this went out for review at the Journal of Translational Medicine in the first place

3/3 Then realize this is a grossly underpowered study using a molecular assay with substantial inherent noise.

To anyone with #MECFS, please ignore this overhyped report, this is unfairly exploiting you.

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling - Journal of Translational Medicine Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, multifactorial disorder characterised by profound fatigue, post-exertional malaise, cognitive impairments, and autonomic dysfunction. Despite its significant impact on quality of life, ME/CFS lacks definitive diagnostic biomarkers, complicating diagnosis and management. Recent evidence highlights potential blood tests for ME/CFS biomarkers in immunological, genetic, metabolic, and bioenergetic domains. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression and cross-tissue exosome signalling. We have previously developed an epigenetic assay, EpiSwitch®, that employs an algorithm-based CCs analysis. Using EpiSwitch® technology, we have shown the presence of disease-specific CCs in peripheral blood mononuclear cells (PBMCs) of patients with amyotrophic lateral sclerosis (ALS), rheumatoid arthritis (RA), prostate and colorectal cancers, diffuse Large B-cell lymphoma and severe COVID-19. In a recent paper, we have identified a profile of systemic chromosome conformations in cancer patients reflective of the predisposition to respond to immune checkpoint inhibitors, PD-1/PD-L1 antagonists, with 85% accuracy. In this Retrospective case/control study (EPI-ME, Epigenetic Profiling Investigation in Myalgic Encephalomyelitis), we used whole blood samples retrospectively collected from n = 47 patients with severe ME/CFS and n = 61 age-matched healthy control patients to perform whole-genome 3D DNA screening for CCs correlating to ME/CFS diagnosis. We identified a 200-marker model for ME/CFS diagnosis (Episwitch®CFS test). First testing on the retrospective independent validation cohort demonstrated a strong systemic ME/CFS signal with a sensitivity of 92% and a specificity of 98%.Pathways analysis revealed several likely contributors to the pathology of ME/CFS, including interleukins, TNFα, neuroinflammatory pathways, toll-like receptor signalling and JAK/STAT. Comparison with pathways involved in the action of Rituximab and glatiramer acetate (Copaxone) (therapies with potential in ME/CFS treatment) identified IL2 as a shared pathway with clear patient clustering, indicating a possibility of a potential responder group for targeted treatment.

2/3 Kudos to @theguardian.com for the link to the research translational-medicine.biomedcentral.com/articles/10....

Scientists develop first ‘accurate blood test’ to detect chronic fatigue syndrome Research could offer hope for ME patients – but some experts urge caution and say more studies needed

1/3 Start by getting highlighted in the @theguardian.com

www.theguardian.com/society/2025...

Using the word in the title to lull people into a false sense of security. It's very devious, I'll admit.

Deaminase-assisted single-molecule and single-cell chromatin fiber sequencing Gene regulation is mediated by the co-occupancy of numerous proteins along individual chromatin fibers. However, our tools for deeply profiling how proteins co-occupy individual fibers, especially at ...

What an amazing assay.

DAF-seq, the evolution of Fiber-seq from the Andrew Stergachis group, using the @pacbio.bsky.social platform:
www.biorxiv.org/content/10.1...

This will revolutionise our understanding of transcriptional regulation and functional non-coding variants.

Ooooh, now we disagree! That proposal only really works if the underlying ambiguity is clarified explicitly ("epigenetics" = each of the following).

In which case, why not leave out the word #epigenetics and just, you know, explain what you mean? It's what humans do with language.

This is how I and @drgmcginty.bsky.social were able to build our careers in the US.

The visa was unique for waiving the 2 year home return for J-1 trainees in Medicine. Congressman Morrison last night told me that was intentional.

We hit the lottery in many ways. Thank you Bruce Morrison.

Plus the genome will have accumulated many more variants than the expected de novo variant (DNV) load of germline cells.

Always worth the periodic reminder about the ambiguity inherent in the word. Lovely work.

By ‘epigenetic’, you mean what?

a. A non-genetic mechanism for inheritance of a trait or phenotype?
b. Something involving transcription regulation?
c. A modifiable cellular memory?
d. Genetic influences on cell differentiation?

Without specifying which, the press release is uninterpretable.

Decades of research have proven that acetaminophen is safe for children when taken correctly and under the guidance of a child’s pediatrician. Learn more.
www.aap.org/en/news-room...

Thank you Jon

Thanks Alexis.

Thanks Kevin.

Thanks Adam

Seven years.
Over 400 pages.
About 750 references.
Over 40 figures.
Finally I get to hold the finished book.
It’s a big day.

#EpigeneticsBook
@cshlpress.bsky.social

Everyone ❤️ Scandinavians

Aluminum-Adsorbed Vaccines and Chronic Diseases in Childhood: A Nationwide Cohort Study: Annals of Internal Medicine: Vol 0, No 0 Background: Aluminum is used as an adjuvant in nonlive vaccines administered in early childhood. Concerns persist about potential associations between vaccination with aluminum-adsorbed vaccines and i...

Public service announcement 2:
www.acpjournals.org/doi/10.7326/...

Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability This nationwide cohort study with sibling control analysis examines the association of acetaminophen use during pregnancy with children’s risk of autism, ADHD, and intellectual disability.

Public service announcement 1:
jamanetwork.com/journals/jam...?

Unhelpful framing. Scientists know we always need to be improving what we do, but science is not “broken”. To suggest this justifies the misplaced destruction of US scientific institutions.

@nytimes.com

I hope the rest of the book makes up for the cover/thanks Kasper

Thanks Cousin Hank! Apparently the Amazon date is correct.

You're right to grab your copy early, I'm confident that this will sell tens of copies!

Under scrutiny -- the Dutch Famine Winter paradigm, the rat maternal licking/grooming model, the vinclozolin transgenerational model, even Waddington's genetic assimilation model.

Extraordinary claims require extraordinary evidence (ECREE: Carl Sagan). I explore how extraordinary the evidence is.

I also highlight some really great new work in the field from @jamiehackett.bsky.social and others as paradigms for how we should be designing updated studies.

But it should be clear that we can't just accept current dogma about DOHaD or transgenerational heritability.

It's awkward to flag these issues, because you can be perceived to be undermining colleagues, which I really wanted to avoid.

Hopefully what will come across is that I try to point out places where we should go back and re-study foundational observations, being open to alternative interpretations.

Probably Chapter 9 'Inheriting Memories'. Digging into the historical foundations of what we believe to be true for intergenerational and transgenerational, non-genetic, 'epigenetic' heritability, it's clear there are weaknesses we don't really acknowledge today.