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Chen, Lijun

Publications and source records attributed to Chen, Lijun.

Multi-scale signaling and tumor evolution in high-grade gliomas

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.

60 APPLIED LIFE SCIENCES↗

Proteogenomic insights suggest druggable pathways in endometrial carcinoma

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

60 APPLIED LIFE SCIENCES↗

Optimal Power Flow With State Estimation in the Loop for Distribution Networks

Here in this article, we propose a framework for running optimal control-estimation synthesis in distribution networks. Our approach combines a primal-dual gradient-based optimal power flow solver with a state estimation feedback loop based on a limited set of sensors for system monitoring, instead of assuming exact knowledge of all states. The estimation algorithm reduces uncertainty on unmeasured grid states based on certain online state measurements and noisy "pseudomeasurements." We analyze the convergence of the proposed algorithm and quantify the statistical estimation errors based on a weighted least-squares estimator. The numerical results on a 4521-node network demonstrate that this approach can scale to extremely large networks and provide robustness to both large pseudomeasurement variability and inherent sensor measurement noise.

24 POWER TRANSMISSION AND DISTRIBUTION↗

An Online Joint Optimization–Estimation Architecture for Distribution Networks

Here in this article, we propose an optimal joint optimization-estimation architecture for distribution networks, which jointly solves the optimal power flow (OPF) problem and static state estimation (SE) problem through an online gradient-based feedback algorithm. The main objective is to enable a fast and timely interaction between the OPF decisions and state estimators with limited sensor measurements. First, convergence and optimality of the proposed algorithm are analytically established. Then, the proposed gradient-based algorithm is modified by introducing statistical information of the inherent estimation and linearization errors for an improved and robust performance of the online OPF decisions. Overall, the proposed method eliminates the traditional separation of operation and monitoring, where optimization and estimation usually operate at distinct layers and different time scales. Hence, it enables a computationally affordable, efficient, and robust online operational framework for distribution networks under time-varying settings.

24 POWER TRANSMISSION AND DISTRIBUTION↗