Spatial proteomics guided by H&E-based AI reveals recurrence-risk niches in triple-negative breast cancer

Deep learning models can predict cancer recurrence from H&E stained slides, but the localized molecular states underlying these predictions remain largely obscured. Here, we developed an outcome informed spatial pathology framework in TNBC that integrates AI generated recurrence risk heatmaps with mass spectrometry based spatial proteomics. In a cohort of 156 patients, distribution based aggregation of high scoring patches achieved an AUC of 0.77 and a C-index of 0.77 in an independent test cohort. Bulk proteomics associated high image derived risk with cell cycle and genome maintenance programs and low risk with immune activation. High and low risk patches coexisted within the same tumor compartment and displayed distinct nuclear and architectural features, revealing intratumoral heterogeneity beyond tissue compartment identity. We then used the heatmaps as coordinate level guides to physically isolate and profile 46 AI defined tumor regions from two recurrence patients. Spatial proteomic profiling revealed a concordant molecular contrast across both patients: mitotic programs were enriched in high risk regions and immune and antigen presentation programs in low risk regions. A 13 protein composite derived from these spatial contrasts showed a trend toward poorer recurrence-free survival with increasing scores in an expanded cohort, while the corresponding transcript based composite stratified recurrence free survival in the independent METABRIC TNBC cohort. Integrating the protein composite with the H&E derived risk score improved the out of bag C-index from 0.679 to 0.739 and enhanced time dependent discrimination at 3 and 5 years. Together, these findings define a new role for outcome trained AI models as spatially explicit experimental guides that connect prognostic morphology with localized molecular states and advance biologically grounded, multiscale biomarker discovery in TNBC.

HyperCLOVA X Technical Report

We introduce HyperCLOVA X, a family of large language models (LLMs) tailored to the Korean language and culture, along with competitive capabilities in English, math, and coding. HyperCLOVA X was trained on a balanced mix of Korean, English, and code data, followed by instruction-tuning with high-quality human-annotated datasets while abiding by strict safety guidelines reflecting our commitment to responsible AI. The model is evaluated across various benchmarks, including comprehensive reasoning, knowledge, commonsense, factuality, coding, math, chatting, instruction-following, and harmlessness, in both Korean and English. HyperCLOVA X exhibits strong reasoning capabilities in Korean backed by a deep understanding of the language and cultural nuances. Further analysis of the inherent bilingual nature and its extension to multilingualism highlights the model's cross-lingual proficiency and strong generalization ability to untargeted languages, including machine translation between several language pairs and cross-lingual inference tasks. We believe that HyperCLOVA X can provide helpful guidance for regions or countries in developing their sovereign LLMs.