Evidence map›Paper›PMID 42546047›Full record

ArticleBriefings in bioinformatics2026

Cross-cohort projection of clinically anchored latent risk enables multi-omics interpretation without refitting.

Zhongfu Huang, Yi Cai, Xiaomei Gao, Shuo Hu, Yongxiang Tang, Minfeng Chen

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Article in Briefings in bioinformatics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Zhongfu HuangDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.
Yi CaiDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.
Xiaomei GaoDepartment of Pathology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008,  China.
Shuo HuDepartment of PET Center, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.ORCID 0000-0003-0998-8943
Yongxiang TangDepartment of PET Center, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.
Minfeng ChenDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.ORCID 0000-0002-2190-1479

Funding

Clinical Big Data System Construction Project Fund of Xiangya Hospital 33020125030Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases (Xiangya) 2022LNJJ,13Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases (Xiangya) 2023LNJJ13Hunan Provincial Science Fund for Distinguished Young Scholars 2024JJ2090Hunan Provincial Science Fund for Distinguished Young Scholars 2024JJ2094National Natural Science Foundation of China 81974397National Natural Science Foundation of China 82170789National Natural Science Foundation of China 82272907Natural Science Foundation of Hunan 2025JJ60616Xiangya Famous Doctor Fund of Central South University 33020123007
6 · The paper itself

Abstract

Linking clinically derived risk signals to reproducible molecular states across independent cohorts remains a major challenge in translational bioinformatics. Existing approaches often rely on cohort-specific model fitting, limiting cross-dataset comparability and downstream biological interpretation. We developed a cross-cohort projection framework that maps baseline clinical variables to a clinically anchored latent risk coordinate, $\mu$, enabling application across external datasets without refitting. The fixed projector was trained in a local imaging cohort and applied unchanged to independent cohorts. Projected $\mu$ was evaluated across multiple molecular layers, including bulk transcriptomics, single-cell-guided deconvolution, spatial transcriptomics, and circulating cell-free DNA (cfDNA). In an independent external cohort, projected $\mu$ preserved separation of time to castration resistance across predefined strata (P = .002), with 30-month risk increasing from 0.13 to 0.86 across ordered $\mu$ bins. In bulk transcriptomics, higher projected $\mu$ was associated with increased proliferation-related signaling and reduced androgen receptor/lineage programs ($\rho$ = 0.40 and -0.26; both P < .001). Deconvolution analyses linked higher projected $\mu$ to reduced AR-high epithelial cell fractions ($\rho$ = -0.17, P = .001). Spatial transcriptomics demonstrated organized tissue-level structure of prespecified molecular programs. In cfDNA, higher projected $\mu$ was associated with a more negative RB1 copy-number signal in the detectable subset ($\rho$ = -0.49, P = .0278). This study presents a projection-based framework for cross-cohort translation of clinically anchored latent risk into interpretable multi-omics context. By enabling reuse of a fixed coordinate without refitting, the approach provides a practical strategy for linking clinical risk to molecular programs and blood-based readouts across datasets.

Indexed as

Computational BiologyProstatic NeoplasmsCell-Free Nucleic AcidsCohort StudiesGene Expression ProfilingHumansMaleMultiomicsSpatial TranscriptomicsTranscriptomeCell-Free Nucleic Acidscell-free DNAclinically anchored latent riskcross-cohort projectionmulti-omics interpretationprostate cancertranslational bioinformatics

Identifiers

PMID42546047
PMCPMC13431287

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.