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PRIME: an interpretable artificial intelligence model based on liquid biopsy improves prediction of progression risk in non-small cell lung cancer
Mil Med Res. 2026 Jan 6;12(1):94. doi: 10.1186/s40779-025-00679-z.
ABSTRACT
BACKGROUND: Despite the predictive impact of circulating tumor DNA (ctDNA) minimal residual disease (MRD), accurate prediction of failure risk after curative-intent treatments for early-stage or localized non-small cell lung cancer (NSCLC) patients to guide personalized therapy remains challenging. This study aimed to develop and validate an interpretable artificial intelligence-assisted model using global data resources.
METHODS: Liquid biopsy data, blood-based genomic alterations, clinicopathological features, and survival outcomes of stage I-III NSCLC patients who underwent surgery or definitive chemoradiotherapy were collected from 6 cohorts. PRIME (Progression Risk prediction by Interpretable Machine learning on ctDNA-MRD, Mutations, and clinical-therapeutic features) was trained by 6 machine learning algorithms across 4 cohorts and validated in 2 independent cohorts. Model performance was evaluated by the area under the curve (AUC) and interpreted by SHapley Additive exPlanations (SHAP). Whole-exome sequencing (WES) or whole-genome sequencing (WGS) of tumor tissue from 430 stage II-III NSCLC patients and RNA-sequencing (RNA-seq) data from 1149 subjects, sourced from The Cancer Genome Atlas, were used to validate the prognostic effect of mutations identified in peripheral blood and investigate the underlying mechanisms.
RESULTS: A global dataset encompassing 781 blood samples from 493 patients was analyzed. Clinical stage, pre-treatment ctDNA, post-treatment MRD, blood-based Kelch-like ECH-associated protein 1 (KEAP1), serine/threonine kinase 11 (STK11), and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations, and treatment modality were significantly associated with the risk of disease progression and were thereby included in the model training. WES/WGS and RNA-seq confirmed the poor prognostic effect of KEAP1, STK11, and CDKN2A mutations, which were characterized by the suppressive tumor microenvironment and attenuated humoral immunity. The neural network (NN) model exhibited optimal prediction of treatment failure risk in the training (AUC = 0.85, 95% CI 0.81-0.89) and validation sets (AUC = 0.82, 95% CI 0.74-0.89). SHAP analysis indicated that MRD (+0.306), treatment modality (+0.128), and pre-treatment ctDNA (+0.043) ranked in the top 3 contributions. NN-PRIME outperformed single liquid biopsy biomarkers and clinical-therapeutic signatures, and demonstrated consistent robustness across different clinical scenarios. High-risk patients identified by NN-PRIME had poorer prognoses but derived significant benefits from adjuvant therapy after surgery.
CONCLUSIONS: As an interpretable model integrating readily-accessible and crucial clinical-genomic predictors, PRIME achieves enhanced performance, allowing for early outcome prediction, refined risk stratification, and personalized clinical decision-making.
PMID:41491583 | PMC:PMC12771999 | DOI:10.1186/s40779-025-00679-z
MemSearcher: Training LLMs to Reason, Search and Manage Memory via End-to-End Reinforcement Learning
Tongyi DeepResearch Technical Report
A Chinese firm has just launched a constantly changing set of AI benchmarks
When testing an AI model, it’s hard to tell if it is reasoning or just regurgitating answers from its training data. Xbench, a new benchmark developed by the Chinese venture capital firm HSG, or HongShan Capital Group, might help to sidestep that issue. That’s thanks to the way it evaluates models not only on the ability to pass arbitrary tests, like most other benchmarks, but also on the ability to execute real-world tasks, which is more unusual. It will be updated on a regular basis to try to keep it evergreen.
This week the company is making part of its question set open-source and letting anyone use for free. The team has also released a leaderboard comparing how mainstream AI models stack up when tested on Xbench. (ChatGPT o3 ranked first across all categories, though ByteDance’s Doubao, Gemini 2.5 Pro, and Grok all still did pretty well, as did Claude Sonnet.)
Development of the benchmark at HongShan began in 2022, following ChatGPT’s breakout success, as an internal tool for assessing which models are worth investing in. Since then, led by partner Gong Yuan, the team has steadily expanded the system, bringing in outside researchers and professionals to help refine it. As the project grew more sophisticated, they decided to release it to the public.
Xbench approached the problem with two different systems. One is similar to traditional benchmarking: an academic test that gauges a model’s aptitude on various subjects. The other is more like a technical interview round for a job, assessing how much real-world economic value a model might deliver.
Xbench’s methods for assessing raw intelligence currently include two components: Xbench-ScienceQA and Xbench-DeepResearch. ScienceQA isn’t a radical departure from existing postgraduate-level STEM benchmarks like GPQA and SuperGPQA. It includes questions spanning fields from biochemistry to orbital mechanics, drafted by graduate students and double-checked by professors. Scoring rewards not only the right answer but also the reasoning chain that leads to it.
DeepResearch, by contrast, focuses on a model’s ability to navigate the Chinese-language web. Ten subject-matter experts created 100 questions in music, history, finance, and literature—questions that can’t just be googled but require significant research to answer. Scoring favors breadth of sources, factual consistency, and a model’s willingness to admit when there isn’t enough data. A question in the publicized collection is “How many Chinese cities in the three northwestern provinces border a foreign country?” (It’s 12, and only 33% of models tested got it right, if you are wondering.)
On the company’s website, the researchers said they want to add more dimensions to the test—for example, aspects like how creative a model is in its problem solving, how collaborative it is when working with other models, and how reliable it is.
The team has committed to updating the test questions once a quarter and to maintain a half-public, half-private data set.
To assess models’ real-world readiness, the team worked with experts to develop tasks modeled on actual workflows, initially in recruitment and marketing. For example, one task asks a model to source five qualified battery engineer candidates and justify each pick. Another asks it to match advertisers with appropriate short-video creators from a pool of over 800 influencers.
The website also teases upcoming categories, including finance, legal, accounting, and design. The question sets for these categories have not yet been open-sourced.
ChatGPT-o3 again ranks first in both of the current professional categories. For recruiting, Perplexity Search and Claude 3.5 Sonnet take second and third place, respectively. For marketing, Claude, Grok, and Gemini all perform well.
“It is really difficult for benchmarks to include things that are so hard to quantify,” says Zihan Zheng, the lead researcher on a new benchmark called LiveCodeBench Pro and a student at NYU. “But Xbench represents a promising start.”
NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance
Nature, Published online: 03 July 2024; doi:10.1038/s41586-024-07620-9
Lactylation of NBS1 by TIP60 promotes homologous recombination-driven DNA repair and resistance to chemotherapy in cancer cells and links altered cancer cell metabolism to increase genome stability.Author Correction: A genomic mutational constraint map using variation in 76,156 human genomes
Nature, Published online: 15 January 2024; doi:10.1038/s41586-024-07050-7
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Cell Death Discovery, Published online: 01 November 2022; doi:10.1038/s41420-022-01219-7
Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p