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Systems pharmacology approaches decipher the anti-cancer efficacy of ethnopharmacological agents in hepatocellular carcinoma

Sci Rep. 2025 Dec 17;15(1):43996. doi: 10.1038/s41598-025-27744-w.

ABSTRACT

Hepatocellular carcinoma (HCC) poses a significant global health burden with limited therapeutic efficacy. Chinese herbal medicines (CHMs) offer multi-target potential, yet their systematic screening and mechanistic elucidation remain challenging. We established a high-throughput multi-omics platform integrating transcriptomics, proteomics, and deep learning (autoencoder and multiple kernel learning) to screen 187 medicinal plants. Five CHMs candidates were identified and shown to modulate hub genes (e.g., AKR1B10, HMGCR, THBS1) and key pathways (TNF/IL-17/MAPK, apoptosis, ferroptosis). Proteomic validation and functional assays confirmed their roles in suppressing proliferation, migration, and inducing apoptosis in HCC cells. This study provides a robust, data-driven pipeline for natural anti-HCC drug discovery, linking specific hub genes to CHM efficacy and offering novel insights into precision ethnopharmacology.

PMID:41408124 | DOI:10.1038/s41598-025-27744-w

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Genomic Next-Token Predictors are In-Context Learners

arXiv:2511.12797v2 Announce Type: replace-cross Abstract: In-context learning (ICL) -- the capacity of a model to infer and apply abstract patterns from examples provided within its input -- has been extensively studied in large language models trained for next-token prediction on human text. In fact, prior work often attributes this emergent behavior to distinctive statistical properties in human language. This raises a fundamental question: can ICL arise organically in other sequence domains purely through large-scale predictive training? To explore this, we turn to genomic sequences, an alternative symbolic domain rich in statistical structure. Specifically, we study the Evo2 genomic model, trained predominantly on next-nucleotide (A/T/C/G) prediction, at a scale comparable to mid-sized LLMs. We develop a controlled experimental framework comprising symbolic reasoning tasks instantiated in both linguistic and genomic forms, enabling direct comparison of ICL across genomic and linguistic models. Our results show that genomic models, like their linguistic counterparts, exhibit log-linear gains in pattern induction as the number of in-context demonstrations increases. To the best of our knowledge, this is the first evidence of organically emergent ICL in genomic sequences, supporting the hypothesis that ICL arises as a consequence of large-scale predictive modeling over rich data. These findings extend emergent meta-learning beyond language, pointing toward a unified, modality-agnostic view of in-context learning.
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