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Tahoe-100M: Mapping drug-induced molecular phenotypes at single-cell resolution

Tahoe-100M is an atlas of 100 million single-cell transcriptomes, capturing how 50 cancer cell lines respond to ∼1,100 drug-dose treatments. By pairing single-cell and molecular phenotypes at scale, the resource links drug mechanisms to cellular responses and provides an openly available substrate for training predictive models of cell behavior.
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An open benchmark and language models for AI in aging biology

LongevityBench, Longevity-LLMs, and Longevity Claw evaluate the readiness of the state-of-the-art AI systems for spearheading aging research.
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Meet a mouse whose brain cortex is made up of human cells

Multiple cameras tracked a mouse as it wandered around a small arena. A computer charted its position and speed, leaving Pong-like traces on a monitor. 

The reason to watch this rodent so carefully? Nearly half its brain volume had been replaced with human cells.

The effort to mix the brain tissues of distant species is being reported today in the journal Nature by a team at Stanford University, led by neuroscientist Sergiu Pașca. 

Pașca’s group previously showed that human brain “organoids”—small blobs of neural tissue—could survive, and even function, after being injected into the heads of baby rodents.

Now, Pașca has taken things a step further by genetically modifying mice so their brains don’t fully develop in the first place. These modified mice are missing most cells of both the cortex and the hippocampus, two key brain areas.

That creates much more room for the human cells to take hold, he says. “Human cells that are placed in these animals will divide, will grow, and within a few weeks to a few months they will take most of that space,” he says. Pașca says one surprising discovery is that the mice lacking brain tissue seemed fairly normal—they walked around and squeaked. But they did have memory problems. In a maze test, they couldn’t remember what parts they’d explored. 

The mice with the added human cells, by contrast, performed better on the maze test. That means the human tissue is playing some role in the animals’ cognition.

Pașca believes what he is calling “xenocortical mice” could be useful in studying brain injuries. However, the report is also a dramatic demonstration of “the combined power of genetic engineering and stem-cell technology to reshape biology,” says Carsten Charlesworth, a scientist who works in a different Stanford lab and was not involved in the research.

Already, brain organoids are being tested in labs to see if they can be connected to computers to play video games. Other scientists have proposed using them like replacement parts to treat stroke victims. 

“What’s most remarkable to me is the extent to which human neural tissue introduced after birth grew and connected with the mouse nervous system across a species barrier,” says Charlesworth. “As these technologies advance, they’ll increasingly force us to challenge our traditional assumptions.”

Last year, Pașca convened a group of ethics experts to study the implications of neural organoid technology, including the odds that an animal could develop human consciousness and the risk that “organoid therapy clinics” might offer scam treatments to desperate patients.

For now, he says, he’s not concerned that the rodents have any type of human cognitive capacities. That is because their brains are relatively tiny and the evolutionary distance between man and mouse is so great. 

But that’s also why Pașca says this type of experiment should not be carried out on higher species: They could end up with large volumes of functioning human brain tissue, potentially blurring the cognitive boundaries between people and animals. 

Pașca specifically cautioned against adding human brain organoids to a monkey engineered to lack a cortex.

“One of the things that I see as a very clear red line is doing this experiment in a primate,” he says. “I don’t think that is justified at this point in any way.”

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Integrated multi-omic profiling enables recurrence risk stratification beyond pathological stage in resected EGFR-mutant lung adenocarcinoma

J Thorac Oncol. 2026 Sep 16:104204. doi: 10.1016/j.jtho.2026.104204. Online ahead of print.

ABSTRACT

BACKGROUND: Early-stage EGFR-mutant lung adenocarcinoma (LUAD) demonstrates heterogeneous outcomes after curative surgery, yet adjuvant treatment decisions are guided by pathological stage alone. Following the ADAURA trial, adjuvant osimertinib is the standard of care for resected stage IB-IIIA EGFR-mutant LUAD; however, real-world data demonstrate that up to 40% of patients remain disease-free at five years without adjuvant osimertinib, underscoring the need for improved risk stratification.

PATIENTS AND METHODS: We performed integrated clinical, genomic and transcriptomic profiling of 400 patients with resected stage IA-IIIA EGFR-mutant LUAD. EGFR-mutant recurrence risk models integrating clinical, genomic and transcriptomic data were developed and validated across one internal and three external cohorts.

RESULTS: Genomic instability, including TP53 co-mutations, copy number alterations and APOBEC-associated mutational signatures, increased with pathological stage. RBM10 co-mutations were enriched in tumours with L858R mutations and correlated with upregulation of WNT signalling and epithelial-mesenchymal transition. Transcriptomic features outperformed clinical or genomic variables alone in predicting recurrence risk, and a multi-omic model demonstrated superior and reproducible performance, achieving a median concordance index of 75.4% across four independent validation cohorts. The multi-omic model stratified recurrence risk within individual pathological stages, including stage I disease, and identified patients most likely to benefit from adjuvant EGFR TKI.

CONCLUSIONS: These findings define the molecular heterogeneity of early-stage EGFR-mutant LUAD and support multi-omic risk stratification to inform adjuvant EGFR TKI decisions beyond pathological stage. Prospective validation in larger cohorts will be required to confirm these findings.

PMID:42749051 | DOI:10.1016/j.jtho.2026.104204

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Type 1 interferon perturbates clonal competition by reshaping human blood development

Nat Genet. 2026 Sep 15. doi: 10.1038/s41588-026-02751-3. Online ahead of print.

ABSTRACT

Inflammation accelerates evolutionary dynamics of hematopoietic stem cells (HSCs) in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasms at baseline and following interferon-α (IFNα) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multiomics methods that distinguish the IFNα effects on mutated stem cells from the admixed wild-type HSCs, with respect to their differentiation, transcriptomes, immunophenotypes and chromatin accessibility. IFNα simultaneously activated HSCs into two polarized states: a lymphoid progenitor expansion associated with an anti-inflammatory state and an inflammatory myeloid progenitor state derived from HSCs. The augmented lymphoid differentiation balanced the typical myeloproliferative-neoplasm-induced myeloid bias, associated with normalized blood counts. Somatic mutations modified the effects of IFNα on HSC differentiation and cell cycle entry rates. Clonal fitness upon IFNα exposure was due to resistance of CALR- or JAK2-mutated stem cells to differentiate into inflammatory myeloid progenitors.

PMID:42745000 | DOI:10.1038/s41588-026-02751-3

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Liquid biopsy for early detection of pancreatic ductal adenocarcinoma

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04625-x

In a prospective study involving 1,785 individuals from four countries, the PANXEON exosome-based biomarker, combined with carbohydrate antigen 19-9 levels, achieves high sensitivity for the detection of early-stage pancreatic cancer.
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Sex-specific biological aging clocks across organs and omics

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04662-6

Sex-specific biological aging clocks across multiple organs and molecular systems show that female and male aging patterns can differ in organ-specific, disease-relevant ways.
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ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway

Cell Death Discovery, Published online: 16 September 2026; doi:10.1038/s41420-026-03349-8

ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway
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AI models need more data about biology, and OpenAI is paying to create it

Last year Ruxandra Teslo, a policy analyst who focuses on clinical trials, posted an idea for supercharging medical AI systems: Use data from failed biotech companies.

By bidding at their bankruptcy proceedings, she proposed, it might be possible to obtain detailed regulatory filings, manufacturing strategies, and safety data—types of information usually considered trade secrets. She called these documents “biotech’s lost archive” and said they could be used to help train AIs that would act as powerful copilots in the often opaque drug approval process. 

Today the OpenAI Foundation, the nonprofit parent of OpenAI, said it would fund her idea as part of a new effort it calls Public Data for Health, which aims to help artificial intelligence make big leaps in medicine by paying to create “high-quality scientific datasets.”

The basic idea is that AI isn’t going to be capable of making important breakthroughs in curing disease unless researchers can feed the models much more information than they have so far. 

“Everyone is recognizing that data is the biggest bottleneck in successfully applying AI to biology,” says Morgan Levine, a former vice president for computation at Altos Labs, a longevity company.

In its initial round of data grants, the OpenAI Foundation also announced that it would give $40 million to a program to collect data about novel cancer vaccines at the University of North Carolina, Chapel Hill, and support OpenAdmet, a group that runs competitions in which researchers try to predict drug effects. 

Teslo’s idea for a biotech archive received $500,000 and will be pursued by 1Day Sooner, an advocacy group representing clinical trial volunteers, which she advises.

“We expect many remaining breakthroughs in preventing and curing disease to come from pairing the intelligence of new models with more observations of the world—in other words, more data,” the OpenAI Foundation said in a statement.

OpenAI started as a nonprofit, but leader Sam Altman restructured it to form a for-profit corporation that develops new models, launches products, and is now planning an initial public offering of stock that could value it at $1 trillion.

Because the foundation holds a 26% equity stake in OpenAI, it is now be on track to become the richest charitable organization on the planet, potentially sitting on $250 billion in stock value. (By comparison, the Gates Foundation and a trust associated with it held about $180 billion at the end of 2025.)  

Making good use of that kind of money will not be easy. The foundation, based in San Francisco, is still hiring for many key roles and started ramping up its grantmaking only this year. Its largest single gift so far, of $100 million, was awarded in August to the Common Health Coalition, an organization that helps patients get access to drugs for hepatitis C.

OpenAI’s charitable efforts come even as apocalyptic fears have broken out about the possibility that runaway AI could wipe out all human life, possibly by launching a deadly bioweapon.

Those fears have been stoked by AI company insiders, some of whom say the chance of human extinction within the next decade is 10% or more. Last week, Altman and xAI founder Elon Musk both endorsed a call by Anthropic CEO Dario Amodei to “slow the pace at which we improve the capabilities of AI models” so that risk prevention can catch up.

Jacob Trefethen, an executive at the foundation, says it essentially operates separately from OpenAI but shares an official mission of ensuring that artificial intelligence “benefits all of humanity.”

“We’re starting grantmaking when we think the best way to achieve that mission is to make grants to external nonprofits, research institutions, and other third parties,” Trefethen said in an interview. He says the foundation hopes to give away $1 billion by the end of the year. 

The $500,000 grant to 1Day Sooner will help the group prove it can obtain the data troves of bankrupt companies, says the organization’s president and cofounder, Josh Morrison. He thinks nonexclusive copies of company datasets could be acquired for only “a few tens of thousands of dollars” each.

His organization is currently in possession of three datasets, two of them donated by Lumen Bioscience, a biotech that previously used the Chapter 11 strategy to gain insights into another company’s drug development efforts. 

Morrison says two other attempts to obtain drug company files this year proved unsuccessful, after 1Day Sooner’s bids were not accepted. 

Bankruptcies could become what some are calling a “new land grab” for AI training. Last month, Google won a bid to take over the corporate data of the failed carrier Spirit Airlines, including 100 million emails. That led to objections from flight attendants and others who worried that private or proprietary data could be exposed. 

The drug company files that 1Day Sooner is seeking are known as common technical documents. They typically contain the back-and-forth between companies and regulators, as well as detailed scientific and medical measurements, and essentially provide everything that is known about a drug.

According to Teslo, who is a writer for Works In Progress and a nonresident fellow at the Institute for Progress, a think tank in Washington, DC, a stockpile of such files could help turn an AI into a regulatory expert, which in her view could be one of the main ways AI helps speed cures to market.

“People say ‘We will invent AI, and AI will cure cancer,’ but that’s very removed from the messy reality and the regulatory process,” she says. “About 70% of the money and time in drug development is spent in clinical development—organizing the trials and testing the drug—but despite that, the process is basically a black box, especially for small biotech companies generating the innovations.” 

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Non-Invasive Assessment of Microvascular Invasion Risk in Hepatocellular Carcinoma Using Liquid Biopsy: Translational Insights and Clinical Implications

Diagnostics (Basel). 2026 Aug 22;16(17):2686. doi: 10.3390/diagnostics16172686.

ABSTRACT

Microvascular invasion (MVI) is a critical prognostic indicator for recurrence and survival in hepatocellular carcinoma (HCC); however, its accurate preoperative assessment remains clinically challenging. Postoperative histopathology is subject to sampling bias and time delays, while traditional imaging techniques lack the molecular specificity required to predict MVI. Liquid biopsy, through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), circulating tumor RNA (ctRNA), and extracellular vesicles (EVs), provides a minimally invasive approach for capturing tumor-derived molecular and cellular signals associated with vascular invasion. This narrative review comprehensively summarizes the current evidence linking these four liquid biopsy analyte categories to MVI in HCC, evaluates their integration into multi-omics predictive models, including multi-marker, clinicopathological-integrated, and imaging-integrated strategies, and proposes an evidence-level framework that categorizes blood biomarkers according to the strength of their support for MVI prediction, distinguishing direct histopathological validation from indirect associations with aggressive tumor biology. Key challenges are critically examined, including the variable specificity of individual biomarkers for MVI, the lack of head-to-head comparative studies, the absence of standardized pre-analytical and analytical protocols, and the methodological limitations of current prediction models. As a narrative review, this work does not employ systematic review methodology, and the evidence synthesis should be interpreted accordingly. The review provides a framework for understanding how liquid biopsy-based MVI risk stratification may inform surgical and perioperative decision-making following prospective validation.

PMID:42739118 | PMC:PMC13564874 | DOI:10.3390/diagnostics16172686

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Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial

Nature Medicine, Published online: 15 September 2026; doi:10.1038/s41591-026-04644-8

In the phase 2 RIO trial, there was delayed viral rebound and resistance to broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS in adult males living with HIV undergoing analytical treatment interruption, and initial reservoir sensitivity to autologous antibodies was associated with a longer time to rebound.
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4D spatiotemporal landscape of mitochondrial phenotypes across cellular states unlocked through representation learning

Agarwal et al. introduce MitoSpace, a self-supervised model trained on 4D lattice light-sheet microscopy data. The model resolves drug-induced mitochondrial phenotypes without labels, predicts membrane potential from morphology and dynamics, generalizes to unseen perturbations and lung organoids, and shows that representation quality improves progressively from 2D to 4D.
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Predicting cellular responses to perturbation across diverse contexts with State

Modeling perturbation effects across large single-cell populations requires flexibility to capture heterogeneity. By training over sets of cells in a shared embedding space, State outperforms baselines at generalizing effects to new contexts. Cell-Eval, the framework used for this comparison, provides a comprehensive benchmark for future models.
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Synthetic transcription factors designed by domain recombination enhance CAR T cell antitumor function

Recombining domains across an entire protein family, rather than relying on natural sequences shaped by evolution, generates synthetic “DESynR” transcription factors with enhanced function. DESynR AP-1 TFs reprogram CAR T cells into non-natural, therapeutically optimized states and outperform natural AP-1 factors in antitumor immunity.
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The sex and reproductive plasticity of intestinal muscles instruct gut size

Adult intestinal size plasticity is driven not only by epithelial stem cells but also by remodeling of the surrounding visceral musculature. Sex- and reproduction-dependent muscle remodeling controls gut size and transit, revealing the intestinal muscle as an active regulator of adult organ adaptation.
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Advancing cancer detection and treatment using longitudinal routine clinical data

Liu et al. develop Oncoformer, a multimodal transformer that reads routine laboratory tests and chest X-rays already collected in everyday care. Across more than 3.6 million individuals, it detects cancer, infers tumor stage, and stratifies treatment response and recurrence risk, pointing toward risk-adapted cancer care built on data already in hand.
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The intrinsic cardiac nervous system is essential for cardiac function and survival

Two genetically distinct neuronal subtypes in the intrinsic cardiac nervous system are differentially required for baseline cardiac function and stress resilience to maintain cardiac stability and survival.
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Spatial proximity sequencing maps developmental dynamics in the germinal center

Sprox-seq enables spatial profiling of protein complexes, surface proteins, and mRNAs in intact tissues by combining proximity ligation with spatial transcriptomics. In human tonsils, Sprox-seq maps germinal center interaction networks, links CD21-CD35 complexes to proliferative programs, reveals interaction-based B cell state transitions, and directly captures B cell-follicular dendritic cell communication.
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