Patients with invasive lobular carcinoma of the breast (ILC) are at high risk of long-term recurrence and metastatic progression with poor prognoses due to delayed detection and treatment-refractory disease. Unfortunately, few models are available to investigate metastatic ILC (mILC) and understand the unique metastatic patterns and phenotypes, including abdominal metastases, leptomeningeal disease, and mixed osteosclerotic/lytic […]

Computational protein design is often constrained by slow, complex, inaccessible, and highly sophiscated and expert-dependent workflows that hinder its transferrability and generalization power for broader applications. We present ProteinMCP, an agentic AI framework designed to accelerate and democratize protein engineering. ProteinMCP automates end-to-end scientific tasks, delivering dramatic gains in efficiency; for instance, a comprehensive protein […]

Post-transcriptional processing has a crucial yet largely unresolved dynamic change and role during the malignant progression of ovarian cancer, especially due to the limited read length of short-read RNA sequencing being insufficient to capture transcript diversity. Here, we performed Iso and RNA sequencing on paired normal, primary tumor, and metastatic samples, generating a comprehensive isoform […]

Spatial transcriptomics enables high-resolution mapping of gene expression in intact tissues but remains challenging due to complex computational workflows that limit accessibility and reproducibility. Here, we present a Model Context Protocol (MCP) framework enabling natural language-driven spatial transcriptomics analysis. By executing analytical tools locally, this architecture eliminates the need to upload massive datasets to large […]

The paradigm of sexual differentiation holds that female embryos retain M&uumlllerian ducts (the precursor to female reproductive tract) by default in the absence of anti-M&uumlllerian hormone (AMH). However, whether M&uumlllerian duct maintenance requires active signaling has remained unclear. Here, we discover that the deletion of mesenchymal Gata2 induces selective regression of the cranial M&uumlllerian duct […]

Electron Microscopy (EM) is widely used in many scientific fields, particularly in life sciences, offering high-resolution information on the ultrastructure of biological organisms. Accurate characterization of EM image quality is important for assessing the EM tool performance, in addition to sample preparation protocol, imaging conditions, etc. This paper provides an overview of tools we developed […]

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas and the most common cause of disease-associated death for Neurofibromatosis Type 1 (NF1) patients. In the context of NF1, MPSNTs develop from benign premalignant precursors. The transition to malignancy is usually accompanied by loss of the polycomb repressive complex 2 (PRC2), leading to aberrant […]

HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) harbors dense lymphocytic infiltration yet responds poorly to immune checkpoint blockade, a paradox whose mechanistic basis remains unresolved. Here we constructed an integrated single-cell and spatial transcriptomic atlas of HPV OPSCC (23,119 cells, 24 cell types), complemented by CRISPR-Cas9 functional validation in two HPV cell lines and multiplex immunofluorescence […]

Ferroptosis is a cell death mechanism characterized by the accumulation of iron-catalyzed lipid peroxides in membrane lipid acyl chains and subsequent loss of membrane integrity.1 Despite thorough investigation of its mechanisms in cultured cells, induction of ferroptosis has unresolved clinical utility in cancer therapy. Here, we systematically evaluate ferroptosis induction via multiple mechanisms, in both […]

Epigenetic regulation governs stem cell fate and perturbations in these mechanisms often lead to tumor development. The CoREST complex, a critical regulator of neural and hematopoietic stem cell differentiation, is recurrently targeted by gain of function mutations in the ubiquitin ligase KBTBD4 in high-risk embryonal brain tumors. However, the tumorigenic potential of these mutations remains […]

Introduction: Implementing target trial emulation (TTE) study methods as end-to-end executable analytic code is technically demanding, and producing standardized, reproducible scripts consistently across research teams remains a persistent challenge. We aimed to develop a framework that translates free-text study descriptions into standardized analytic specifications and executable Strategus R scripts for the Observational Health Data Sciences […]

Causal effects in complex traits are typically represented by a single linear slope. While conventional Mendelian randomization (MR) provides efficient scalar estimates, projection-based summaries do not explicitly capture structural organisation in joint effect space under genetic heterogeneity. We introduce MR-UBRA (Mendelian randomization-Unified Bayesian Risk Architecture), a probabilistic framework that decomposes instrumental variants into genetic risk […]