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Lu, Youyong

Publications and source records attributed to Lu, Youyong.

A prognostic risk model for glioma patients by systematic evaluation of genomic variations

The overall survival rate of gliomas has not significantly improved despite new effective treatments, mainly due to tumor heterogeneity and drug delivery. Here, we perform an integrated clinic-genomic analysis of 1, 477 glioma patients from a Chinese cohort and a TCGA cohort and propose a potential prognostic model for gliomas. We identify that SBS11 and SBS23 mutational signatures are associated with glioma recurrence and indicate worse prognosis only in low-grade type of gliomas and IDH-Mut subtype. We also identify 42 genomic features associated with distinct clinical outcome and successfully used ten of these to develop a prognostic risk model of gliomas. The high-risk glioma patients with shortened survival were characterized by high level of frequent copy number alterations including PTEN, CDKN2A/B deletion, EGFR amplification, less IDH1 or CIC gene mutations, high infiltration levels of immunosuppressive cells and activation of G2M checkpoint and Oxidative phosphorylation oncogenic pathway.

60 APPLIED LIFE SCIENCES↗

Exposing structural variations in SARS-CoV-2 evolution

The mutation of SARS-CoV-2 influences viral function as residue replacements affect both physiochemical properties and folding conformations. Although a large amount of data on SARS-CoV-2 is available, the investigation of how viral functions change in response to mutations is hampered by a lack of effective structural analysis. Here, we exploit the advances of protein structure fingerprint technology to study the folding conformational changes induced by mutations. With integration of both protein sequences and folding conformations, the structures are aligned for SARS-CoV to SARS-CoV-2, including Alpha variant (lineage B.1.1.7) and Delta variant (lineage B.1.617.2). The results showed that the virus evolution with change in mutational positions and physicochemical properties increased the affinity between spike protein and ACE2, which plays a critical role in coronavirus entry into human cells. Additionally, these structural variations impact vaccine effectiveness and drug function over the course of SARS-CoV-2 evolution. The analysis of structural variations revealed how the coronavirus has gradually evolved in both structure and function and how the SARS-CoV-2 variants have contributed to more severe acute disease worldwide.

59 BASIC BIOLOGICAL SCIENCES↗