Umber Dube

The fate of melanocytes and the disorganization of basement membrane in a guinea pig model of Rhododendrol-induced chemical vitiligo Background : Rhododendrol (RD) is a phenolic compound that was first developed as a skin-lightening agent that occasionally induces skin depigmentation. Although it has been shown that RD induces mela...

"These findings suggest that RD-induced alterations in basement membrane structure may contribute to melanocyte detachment and loss, which is the cause of skin depigmentation not only in RD-induced vitiligo but also in vitiligo."

www.biorxiv.org/content/10.1...

Conservation and divergence of metabolic phenotypes between patient tumours and matched xenografts - Nature Metabolism Rao and Cai et al. perform a detailed metabolic comparison between primary tumours from patients and their matching xenografts, which identify conserved as well as divergent metabolic patterns.

1/Patient-derived xenografts (PDXs) are used in preclinical testing of cancer therapies, including metabolic therapies. We determined which metabolic properties are retained, and which are lost, when melanomas from patients are implanted and passaged as PDXs in mice.
www.nature.com/articles/s42...

Structural variants are significant contributor to autism. But many SVs & TRs are hard to detect with short reads. Long read sequencing with @pacbio.bsky.social and @nanoporetech.com captures and maps out alot of what short reads miss. So what can LR-WGS tell us about autism? 🧵

📣 Latest from the lab: Performance of deep-learning-based approaches to improve polygenic scores www.nature.com/articles/s41...

Its thought deep learning will substantially improve PGS but the reality is MANY have tried but no/little gain has been seen so far. Here we report our negative results.

A very interesting finding is the robust increase in ancestral diversity in younger participants, suggesting that the US population has become more genetically diverse over time.

🔗link to study: nature.com/articles/s41...

Latin-American genetic data available securely to approved researchers worldwide/Datos genéticos latinoamericanos disponibles para investigadores de todo el mundo

Big news for health data research and population diversity: The Mexico City Prospective Study data are now available securely to approved researchers worldwide. www.ndph.ox.ac.uk/news/latin-a...

Cohort description: www.ctsu.ox.ac.uk/research/pro...

GitHub - ArcInstitute/xsra: An efficient CLI to extract sequences from the SRA An efficient CLI to extract sequences from the SRA - ArcInstitute/xsra

Extracting @NCBI SRA files with fasterq-dump can require 17x the size of the accession while decompressing. Our new tool xsra extracts sequences at 5x throughput with significantly less disk usage, built-in compression, and optional BINSEQ outputs

github.com/arcInstitute...

Massive multi-ancestry GWAS resource for 1,167 clinical traits & diseases in 6 global biobanks (n=1,789,365)

👉29,139 locus-trait pairs
👉2,624 non-overlapping loci across the genome
👉associated with 6 traits each (median)
👉colocalization across traits for 72% of loci [1/3]

Thanks to @misharosenbach.bsky.social for amplifying NEJM's call for submissions for this collection to #DermSky

CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade - Nature Medicine Analysis of multiple cohorts of patients with melanoma demonstrates a positive association between cytomegalovirus serostatus and overall survival in patients treated with monotherapy but not combinat...

Why you should know your viral exposure status (i.e CMV) if you're going to undergo immunotherapy for cancer (but almost no one knows)
www.nature.com/articles/s41...

Very excited to share our preprint led by M. Levin @skoyama.bsky.social J. Woerner & with S. Damrauer assessing genome-wide pleiotropy of >1,000 clinical traits across ~1.7M individuals with nearly 30K locus-trait associations!
www.medrxiv.org/content/10.1... @medrxivpreprint.bsky.social

Methodological issues in visible LED therapy dermatological research and reporting

Methodological issues in visible LED therapy dermatological research and reporting

"... fluences, wavelengths, and solar exposure equivalent differed by orders of magnitude ..., with effective doses often comparable to typical daily solar exposure."

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

Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma Alpha-synuclein, a neurodegeneration-associated protein, functions in nucleolar DNA double-strand break repair in melanoma.

Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma | Science Advances www.science.org/doi/10.1126/...

This study is a big deal. Is it going to be the one that kicks down the PRS door? Maybe. And that’s saying something.

Assessment of a Polygenic Risk Score in Screening for Prostate Cancer www.nejm.org/doi/full/10....

Skin injury releases damage-encoded systemic signals that can initiate immunity to novel antigens introduced at distal barrier sites @sciimmunology.bsky.social
www.science.org/doi/10.1126/...

How population stratification led to a decade of sensationally false genetic findings Stratification makes environments look like genes

I wrote about how population stratification in genetic analyses led to a decade of false findings and almost certainly continues to bias emerging results. But we are starting to have statistical tools to sniff it out. A 🧵:

Dietary L-3,4-dihydroxyphenylalanine (L-DOPA) augments cuticular melanization in Anopheles mosquitos while reducing their lifespan and malaria parasite burden https://www.biorxiv.org/content/10.1101/2024.09.30.615839v1 L-3,4-dihydroxyphenylalanine (L-DOPA), a naturally occurring tyrosine derivative, is prevalent in en

Dietary L-3,4-dihydroxyphenylalanine (L-DOPA) augments cuticular melanization in Anopheles mosquitos while reducing their lifespan and malaria parasite burden https://www.biorxiv.org/content/10.1101/2024.09.30.615839v1

Clinical outcomes and genomic profiles of MAP2K1-mutated primary cutaneous melanocytic tumours Class I MAP2K1 mutations typically occur alongside other MAPK pathway mutations and may contribute to aggressive melanoma behaviour. In contrast, Class II and III MAP2K1 mutations can independently dr...

An interesting paper describing a class of intermediate melanocytic neoplasms driven by MAP2K1 mutations. www.thelancet.com/journals/ebi...

G-quadruplexes and their unexpected ability to fold proteins | PNAS G-quadruplexes and their unexpected ability to fold proteins

Have a look at our newest commentary in @pnas.org :

"G-quadruplexes and their unexpected ability to fold proteins"

Full text: www.pnas.org/doi/10.1073/...

#G4 #quadruplex #proteins #folding

📣Excited to share my last postdoc paper with
@soumya-boston.bsky.social on eQTL mechanisms depending on where the RNA is in the cell! @broadinstitute.org @harvardmed.bsky.social
TL;DR:Early RNA eQTL variants in the nucleus and late RNA eQTL variants in the cytosol have distinct molecular mechanism🧵

Key reads from last week on human genetics, multiomics, and precision medicine 🧵

1⃣New e/sQTL resource from TOPMed

In 14,324 whole blood & tissue samples the study detects cis- and trans-e/sQTLs and colocalizes them with 10,000 GWAS signals for 164 traits.

🔗 www.medrxiv.org/content/10.1...

🚨NEW PAPER! Together with Wuno Akingbuwa (@wonuola.bsky.social) we developed a way to estimate non-linear genetic correlations. It didnt sit well with us that known non-linear relations (e.g. BMI and MDD with a famous U shaped ) are poorly captured in statistical genetics. 🧵

The distribution of highly deleterious variants across human ancestry groups A major focus of human genetics is to map severe disease mutations. Increasingly that goal is understood as requiring huge numbers of people to be sequenced from every broadly-defined genetic ancestry...

“The distribution of highly deleterious variants across human ancestry groups”. Preprint with Anastasia Stolyarova and @gcbias.bsky.social: www.biorxiv.org/content/10.1...

Multi-ancestry meta-analysis of keloids uncovers novel susceptibility loci in diverse populations https://www.medrxiv.org/content/10.1101/2025.01.28.25321288v1

Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation Itch is a dominant symptom in dermatitis, and scratching promotes cutaneous inflammation, thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and wheth...

Why scratching makes a rash worse and a potential benefit to scratching--it reduced S. aureus on skin. Andrew Liu's paper from our lab is out now at #science #neuroimmune #immunology www.science.org/doi/10.1126/...

A genome-wide atlas of human cell morphology - Nature Methods An optical pooled cell profiling platform (PERISCOPE) based on Cell Painting and optical sequencing of molecular barcodes was used to develop the first unbiased genome-wide morphology-based perturbati...

Our paper “A genome-wide atlas of human cell morphology” is finally out today in @naturemethods.bsky.social ! www.nature.com/articles/s41...

(I tweeted about our preprint in 2023 over at the bad place, but deactivated my account, so here we go again!)

Another benefit is avoiding prior authorizations for relatively inexpensive and highly effective medications.

I'm just here for the melanistic morph of the eastern quoll.

But also it's really cool that the genes at play here are the same ones that come up in human GWAS of pigmentation.

Keratin intermediate filaments mechanically position melanin pigments for genome photoprotection Melanin pigments block genotoxic agents by positioning on the sun-exposed side of human skin keratinocytes nucleus. How this position is regulated and its role in genome photoprotection remains unknow...

Keratin intermediate filaments mechanically position melanin pigments for genome photoprotection www.biorxiv.org/content/10.1...

Today we report that an engineered skin bacterium, swabbed gently on the head of a mouse, can unleash a potent antibody response against a pathogen. Could lead to topical vaccines that are applied in a cream. @djenetbousbaine.bsky.social led the charge... @natureportfolio.bsky.social 1/55