Zhiyuan Hu

Year 2 Graduate Student Prize Winner

When studying my BSc in Biological Sciences at Peking University, I was encouraged to take courses in mathematical modeling and bioinformatics and I worked on the comparative analysis of bacterial genomes in Prof Huaiqiu Zhu’s Bioinformatics group. My interest extended to single-cell transcriptomes during my NDM summer internship in Oxford with Dr Quin Wills and Dr Christopher Yau. This experience inspired me to apply for my current DPhil project.

Supported by the CSC-NDM studentship, I started my DPhil in Oxford with my supervisors, Dr Christopher Yau and Prof Ahmed Ahmed. My primary research involves using single-cell RNA sequencing to examine early changes in ovarian cancer, which involves both wet lab work and computational analysis.

However, at the end of my first Michaelmas term, Ahmed showed me a very intriguing phenomenon that, in the ovarian cancer samples, if the TP53 harbours a nonsense mutation, its mRNA is degraded and its expression drops significantly due to the nonsense-mediated decay pathway. And thus, I begun a “side project” which ran alongside my main DPhil research.

We investigated the global impact of nonsense-mediated decay in cancer by developing an algorithm to predict which genomic mutations can elicit the nonsense-mediated decay of the corresponding mutated mRNA. We applied this algorithm to the data from five cancer types in the Cancer Genome Atlas (TCGA) and then expanded our studies to 24 cancer types examing 7,725 cancer genomes. To facilitate the use of our algorithm, I wrote it into an R package to functionally annotate the genomic mutations which is now being used by other research groups to complete similar analyses. We submitted our manuscript and this was subsequently accepted for publication in Nature Communications (Hu, Yau and Ahmed, 2017 https://www.nature.com/articles/ncomms15943)

I am now focused on my main DPhil research which has led me to sequenced over one thousand single cells in ovarian cancer patients. My goal is to identify new biomarkers for different cell populations including ones that may be early initiators for the disease. I hope to be able to identify molecular targets that could be used to enable early detection of this disease which is usually only caught at an advanced stage.

Studying in Oxford is an invaluable experience in my life. I sincerely appreciate the support and assistance from my department, my colleagues and my excellent supervisors. I look forward to working with and learning from them in the next two years.

Publications

Hu, Z., Yau, C. & Ahmed, A. A. A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay. Nat Commun 8, 15943 (2017).