An agentic system for rare disease diagnosis with traceable reasoning | Nature Rare diseases affect more than 300 million people worldwide1–3, yet timely and accurate diagnosis remains an urgent challenge1,3–5. Patients often endure a prolonged ‘diagnostic odyssey’ exceeding 5 years, marked by repeated referrals, misdiagnoses and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burden4,5. Here we present DeepRare—a multi-agent system for rare disease differential diagnosis decision support6–8 powered by large language models, integrating more than 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured human phenotype ontology terms and genetic testing results to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare d

DeepRare transforms rare disease diagnosis. It cuts the 5+ year "diagnostic odyssey", reducing emotional and economic costs for 300M affected globally. PMID:41708847, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-10097-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Base barrier cells provide compartmentalization of choroid plexus, brain and CSF | Nature Neuroscience The choroid plexus (ChP), located in the brain ventricles, is largely composed of ChP epithelial cells that produce the cerebrospinal fluid (CSF) and form the blood–CSF barrier. At the ChP–brain attachment sites, we have discovered unique fibroblasts referred to as ChP base barrier cells (BBCs). We show that ChP BBCs originate from meningeal mesenchymal precursors, arrive early during development, remain throughout life and are conserved across species. ChP BBCs are transcriptionally similar to meningeal arachnoid barrier cells and are interconnected by both adherens and tight junctions. Notably, we provide evidence that the BBCs function as a barrier, controlling communication between the periphery and central nervous system. Moreover, during inflammatory insult, we observed a loss of barrier integrity and immune cell crossing. Altogether, our research revealed a barrier at the ChP base, crucial in protecting the central nervous system by compartmentalizing the ChP stroma, brain paren

Choroid plexus base barrier cells, derived from meningeal mesenchymal precursors, form blood-CSF barrier, exist lifelong! PMID:41680326, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-025-02188-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamadermatol.2025.6123 No description available

Man in 90s: granulomatous dermatitis treated with topical delgocitinib. Successful outcome highlighted in JAMA Derm report! PMID:41811334, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2025.6123 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

This case study shows how integrated #RNA-seq and whole exome sequencing support mechanism-of-action validation in early oncology trials.
See what we found out! 👀
www.fiosgenomics.com/wes-and-rna-seq-analysis...

#bioinformatics

https://doi.org/10.1001/jamadermatol.2026.0042 No description available

Preventing HFS in cancer patients: A meta-analysis of 21 RCTs shows promise in pharmacologic strategies against chemotherapy-induced HFS. PMID:41779386, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0042 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cardiotoxicity of T cell immunotherapies | Nature Reviews Cardiology T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and

T cell immunotherapies, like CAR T cells and bispecific antibodies, boost cancer treatment but can risk heart toxicity. PMID:41730987, Nat Rev Cardiol 2026, @NatRevCardiol https://doi.org/10.1038/s41569-026-01265-z #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamadermatol.2026.0217 No description available

AI's potential in melanoma diagnostics explored: Analysis of dermoscopy, AI, and AI-assisted dermatology shows promising results for future clinical use. PMID:41879756, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0217 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Using #SingleMolecule imaging we find that TFs:

-boost co-transcriptional #ribosomal #RNA processing!

-their binding #dynamics fundamentally differ for mRNA (transient) versus rRNA #transcription (stable)!

@biorxivpreprint.bsky.social Anastasiia Chaban @embl.org

www.biorxiv.org/content/10.6...

Post-pandemic changes in population immunity have reduced the likelihood of emergence of zoonotic coronaviruses | Nature Communications Infections by endemic viruses, and the vaccines used to control them, often provide cross-protection against related viruses, potentially altering the transmission dynamics and likelihood of emergence of new zoonotic viruses with pandemic potential. Here, we investigate how population immunity after the COVID-19 pandemic has impacted the likelihood of emergence of a novel sarbecovirus, termed SARS-CoV-X. To this end, we combined empirical cross-neutralisation data with mathematical modelling to identify key immunological and epidemiological factors shaping sarbecovirus emergence. We show that sera from individuals with different COVID-19 immunological histories contained cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses. Simulations parameterised by these data predict that the likelihood of emergence of a novel sarbecovirus has been reduced significantly by population cross-immunity, with outcomes determined by the extent of cross-protectio

Post-COVID population immunity lowers new zoonotic coronavirus risk. Study: Cross-neutralization data + models show reduced SARS-CoV-X threat. PMID:41876522, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69988-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation | Nature Chemical Biology Subcellular stress profoundly influences protein synthesis. However, both the nature of spatiotemporally restricted chemical cues and local protein responders to these cues remain elusive. Unlocking these mechanisms requires the ability to functionally map in living systems locale-specific stress responder proteins and interrogate how chemical modification of each responder impacts proteome synthesis. We resolved this problem by integrating precision localized electrophile generation and genetic code expansion tools. Upon examination of four distinct subcellular locales, only nuclear-targeted electrophile stress stalled translation. We discovered that NCBP1—a nuclear-resident protein with multifaceted roles in eukaryotic mRNA biogenesis—propagated this nuclear stress signal through a single cysteine (C436) from among its 19 conserved cysteines. This NCBP1(C436)-specific modification elicited alternative splicing of more than 250 genes. Mechanistically, global protein synthesis stall wa

NCBP₁ stress signaling alters S6K₁ splicing, hindering translation. Researchers integrated localized electrophile methods. PMID:41667655, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-025-02135-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cardiomyocyte Cyclin-dependent kinase 9 directly binds to and phosphorylates NF-κB p65 subunit to drive cardiac inflammation and remodeling | Nature Communications Hypertensive heart failure highlights an urgent need for effective therapeutic strategies. Protein kinases regulate multiple pathways in cardiac pathophysiology and may provide promising therapeutic targets. Here, we identified a Cyclin-dependent kinase, CDK9, promoting inflammation and cardiac remodeling in terminally differentiated cardiomyocytes. Firstly, kinase enrichment analysis and experimental evidence revealed CDK9 phosphorylation at Thr-186 in both human and mouse hypertrophic heart tissues. CDK9 loss of function via T186A mutation in cardiomyocytes attenuated Ang II-induced heart remodeling and NF-κB-mediated inflammation, whereas CDK9 overactivation by T186E mutation induces. This regulatory function of CDK9 in cardiac remodeling is cell cycle-independent. Further studies demonstrate that the kinase domain of CDK9 directly binds to NF-κB P65 protein, which leads to the CDK9/P65 complex nuclear translocation, P65 phosphorylation, and transcription of inflammatory and hypertr

CDK9 phosphorylates NF-κB p65 in cardiomyocytes, fueling inflammation and remodeling in hypertensive heart failure. Potential target: Thr-186 site. PMID:41876530, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70410-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://www.cell.com/cell/fulltext/S0092-8674(25)01495-3 No description available

EBV alters the transcriptome and immunopeptidome in HLA-DR15+ B cells, enhancing myelin peptide presentation, potentially driving MS pathogenesis. PMID:41534530, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

#RNA therapy 😲

scitechdaily.com/a-simple-injection-could...

Proteomic landscape of Ewing sarcoma primary tumors and metastases | Nature Communications Ewing sarcoma (EWS), a rare pediatric bone tumor, poses unique therapeutic challenges due to its distinct microenvironment and limited molecular understanding. To gain a comprehensive molecular and functional view of the tumors in their microenvironment, we perform a deep mass spectrometry-based proteomic analysis of 170 tumor samples from 74 patients from primary, relapsed, and metastatic tumors. Analysis of more than 10,000 proteins across patients reveals insights into cancer prognosis, chemo-resistance, and progression. Our analyses suggest that ferroptosis pathways may be associated with chemotherapy response in EWS, and we delineate molecular subclasses that correlate the tumor immune landscape with DNA damage repair, ubiquitin-related proteins, and patient outcomes. Multiplexed immunofluorescence imaging indicates possible associations between neutrophils and poorer prognosis, and between macrophages/T cells and a more favorable prognosis. Altogether, this investigation provides

Ewing sarcoma proteomics: 10,000+ proteins studied in 170 tumor samples from 74 patients, offering key insights into prognosis and chemoresistance. PMID:41813675, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70449-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

The silent majority: RNAs that don’t make proteins Once considered cellular junk, non-coding RNAs are emerging as key players in everything from brain development to cancer — with much still to be discovered

“Non-coding RNAs turn out to regulate everything from embryonic development to immune responses to brain function. They help determine which genes get turned on and off, and when. They can promote cancer or suppress it.”
#Science #Scicomm #RNA #MedSky
knowablemagazine.org/content/arti...

The silent majority: RNAs that don’t make proteins Once considered cellular junk, non-coding RNAs are emerging as key players in everything from brain development to cancer — with much still to be discovered

Dr. Jeremy Wilusz and other experts talk about non-coding RNA. #RNA

Mast cell extracellular granules are bioactive condensates assembled by heparin and polyamine | Nature Chemical Biology Biomolecular condensates are membraneless bodies that organize biochemical reactions typically within cells. However, the roles of condensates in extracellular space—where conditions differ substantially from intracellular space—remain poorly understood. Here we report that mast cell extracellular granules (MCEGs), a stable membraneless entity, are condensates assembled through electrostatic interactions between glycosaminoglycans and polyamines. Disrupting polyamine synthesis or trafficking blocks MCEG formation and compromises the storage of proteases and cytokines. Granules reconstituted with heparin and spermine are sufficient to enrich mediators such as carboxypeptidase A3 (CPA3) and tumor necrosis factor (TNF), maintaining an elevated pH and higher concentrations of calcium and zinc compared to the extracellular milieu. This unique environment enhances CPA3 enzymatic activity. Furthermore, the granules increase TNF binding and its bioactivity toward endothelial cells. Together, w

Mast cell extracellular granules (MCEGs) are bioactive condensates formed by heparin and polyamines, crucial for immune responses. PMID:41760814, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-026-02165-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Critical Assessment of a Structure-Based Pipeline for Targeting the Long Noncoding RNA MALAT1 Long noncoding RNAs (lncRNAs) are increasingly recognized as druggable targets due to their conserved secondary/tertiary structures and regulatory roles in disease. A prototypical example is the MALAT...

🧬 lncRNA #MALAT1 as a case study to test docking on flexible #RNA targets for #drugdiscovery. HREX MD revealed two sites, whose druggability was assessed through ensemble docking of 21 diminazene derivatives and multiple scoring functions. @JCIM pubs.acs.org/doi/10.1021/...

https://doi.org/10.1126/science.aea1820 No description available

Discover MULTI-evolve: a rapid evolution method efficiently engineering protein multimutants using AI. Transform lengthy, costly trials! PMID:41712694, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aea1820 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

RNA-specific local translation is patterned by condensates for multinucleate cell growth | Nature Cell Biology Coordination between growth and nuclear division is a common cell feature. In some syncytia, nuclei divide asynchronously throughout the cell but growth occurs only at discrete locations, raising the question how the processes are locally regulated and globally coordinated. In the syncytial fungus Ashbya gossypii, both cell cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. Here we show that Whi3 condensates are enriched for translation regulators and are associated with local, spatially patterned translation of specific target RNAs near nuclei and growth sites. Whi3–RNA condensates can both promote and repress mRNA translation in an RNA- and condensate size-dependent manner in vitro. Condensate interfaces are sites of translation, tunable by condensate composition, RNA valency and protein charge state in vitro. Together, these data suggest that Whi3 condensates can generate a continuum of translation states tha

In Ashbya gossypii, Whi3 protein forms RNA condensates to synchronize nuclear division and growth in multinucleate cells. PMID:41772090, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01887-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamadermatol.2026.0181 No description available

Discover the promise: Intralesional interleukin-2 therapy shows potential in treating high-risk or sensitive cSCC cases! 🎯📊 PMID:41848721, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0181 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule | Nature Communications The kidney proximal tubule is a highly specialized epithelium that transports metabolites and maintains body homeostasis. Cells lining this nephron segment are densely packed with lysosomes, but little is known about the dynamic activity of these organelles in situ. Here, using targeted sensors and live cell and intravital imaging we track acidified lysosomes along the mouse proximal tubule and uncover marked axial heterogeneity in their distribution, characteristics and organellar interactions. In the early part, cathepsin-rich lysosomes frequently contact with apical endosomes to receive and catabolize filtered plasma proteins. Conversely, in the later region, lipase-containing lysosomes traverse cells to mobilize and degrade mitochondria-associated lipid droplets and facilitate their extrusion into the tubular lumen. Acutely de-acidifying lysosomes dramatically alters their movement, causing major changes in tubular protein and lipid processing. Thus, lysosomes in proximal tubules a

Kidney proximal tubule lysosomes show dynamic, axial heterogeneity revealed via live imaging—marked differences in distribution and interactions observed.🚀 PMID:41803103, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70306-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

We are heading to #ABRF2026 in Pittsburgh, PA (March 28-31)!

Visit us at Booth #716 to explore solutions designed to support core facilities and streamline workflows for university research labs.

Let’s connect and discuss how we can help enhance your lab’s efficiency.

#NGS #DNA #RNA #RNAseq

https://doi.org/10.1093/nar/gkag226 No description available

Genome-wide CRISPR screens reveal the EXO1-CAF-1 pathway mitigates R-loop DNA damage, critical for repair and cisplatin response. PMID:41841497, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag226 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Magnaporthe oryzae MoPh1 perceives ER stress and promotes adaptive responses via a plasma membrane-to-vacuole pathway | Nature Communications During growth and development, cells experience both internal and external stresses, which can exert harmful impacts if they are poorly managed. Endoplasmic reticulum (ER) stress is an internal stress that is induced when protein misfolding or perturbations occur at excess rates, and the conventional response pathways from the ER to the nucleus are activated to address the stress. However, the involvement of the plasma membrane (PM) system in response to this internal stress has been insufficiently investigated. Here, a PM sensor, MoPh1, was observed to perceive stress through ER-PM contact sites and target the autophagosome and vacuole, consequently stimulating the autophagy process and supporting stress relief. The PM-to-vacuole pathway mediated by MoPh1 is independent of the classical ER-to-nucleus pathway and might be highly important in both fungi and plants, as it plays a crucial role in alleviating ER stress and promoting cellular adaptation for cell survival. The unfolded prote

Discovery: Magnaporthe oryzae MoPh1 detects ER stress and boosts adaptive responses via a novel plasma membrane-vacuole route, enhancing stress management! PMID:41839901, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70610-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1126/science.adr4661 No description available

Study in Science: Myelin in zebrafish and rodents swells before damage but can recover via remodeling. High neuron activity worsens damage. PMID:41678629, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adr4661 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

The Approval of Redemplo for Familial Chylomicronemia Syndrome and the Many Flavors of GalNAc-Oligonucleotides - PubMed In the fourth quarter of 2025, a press release announced the approval of the eighth small interfering RNA (siRNA)-based therapeutic. Redemplo (plozasiran), developed by Arrowhead Pharmaceuticals, is…

Hot off the press from the Alterman & Khvorova labs: The Approval of Redemplo for Familial Chylomicronemia Syndrome and the Many Flavors of GalNAc-Oligonucleotides

buff.ly/chHxiUY #RNA #RNATherapeutics @UMassChan

A bedazzled DeNovix DS-11 FX+ Spectrophotometer / Fluorometer on the Biozym Scientific booth at Analytica 2026.

Andrew Jones and Charlie Forward smile in front of a bedazzled DeNovix DS-11 FX+ Spectrophotometer / Fluorometer on the Biozym Scientific booth at Analytica 2026.

Attendees at Analytica 2026 chat by the Biozym Scientific booth.

We've had a great time at #Analytica! We also had a very special DS-11 FX+ displayed on the Biozym booth to celebrate our recent Diamond Seal of Quality from SelectScience.

Enter our giveaway: go.denovix.com/sm-diamond

#Analytica2026 #LifeScience #Laboratory #DNA #RNA

Divalent siRNA for prion disease - PubMed Prion protein (PrP) lowering is effective in animal models of prion disease and is being tested clinically in prion disease patients, but there remains a need for more potent PrP-lowering drug candidates....

Hot off the press from the RTI: Divalent siRNA for prion disease
pubmed.ncbi.nlm.nih.gov/41867745/?ut... #RNA #RNATherapeutics

https://www.cell.com/ajhg/fulltext/S0002-9297(26)00070-4 No description available

Breakthrough in detecting de novo variants: duoNovo identifies them in 1 parent & proband; 104 trios sequenced with PacBio HiFi! #Genetics PMID:41795468, Am J Hum Genet 2026, @AJHGNews www.cell.com/ajhg/fulltext/S0002-9297... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪