A global digital navigator of human health for precision medicine.
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Journal Article↗
Biomedical subjects
Xian Shen
Publications and source records attributed to Xian Shen.
Advancing cancer detection and treatment using longitudinal routine clinical data.
Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.
Humans↗
The TONSL-MMS22L complex and FANCM form an interdependent complex on chromatin to counter replication stress.
FANCM is branchpoint DNA translocase essential for cellular response to replication stress. Here, we show that replication stress stimulates FANCM and the TONSL-MMS22L heterodimer bound to histones H3-H4 to form an interdependent complex on chromatin. TONSL-MMS22L recruits FANCM and Fanconi anemia (FA) core complex to stalled and collapsed forks, maintains FANCM on replication-stressed chromatin, promotes FANCD2 monoubiquitination, facilitates both repair and replication traverse of DNA interstrand crosslinks (ICLs), and suppresses sister chromatid exchanges, through its interactions with FANCM and H3-H4. Reciprocally, both DNA translocase activity and phosphorylation of FANCM facilitate recruitment of TONSL-MMS22L and RAD51 to perturbed forks. Moreover, TONSL-MMS22L and FANCM function together to promote activation of the FA pathway, ICL repair, homologous recombination and replication traverse. Cancer patients with tumors with wildtype FANCM and low expression of TONSL-MMS22L have a more favorable prognosis than those with high expression. Thus, FANCM-TONSL-MMS22L acts coordinately as a complex on chromatin that resolves replication stress, and this complex may present a therapeutic target for wildtype FANCM-linked cancer.
FANCM↗