Identification of the Ischemic Pathway Level Changes by Integrating Temporal Phosphoproteome in Ovarian Cancer

Budak, Gungor
Fraenkel, Ernest
Tunçbağ, Nurcan
The temporal proteome studies aim to evaluate changes in the proteome and phosphoproteome when there is a delay in freezing tissues following tumor excision. Cold ischemia corresponds to the delay time to freezing post-excision. Recently, Carr and his colleagues have shown that ischemia does not affect the global proteome, but the phosphoproteome shows 10% change during ischemia. In this work, we use this published phosphoproteomic dataset derived from tumors of four ovarian cancer patients where the samples are frozen without any delay and with a delay of 5, 30 and 60 minutes [1]. We first analyzed the post-excision phosphorylation changes across different patients and showed that the ischemic effect is very heterogeneous at phosphoproteomic level. Then, we reconstructed patient-specific network models by inferring the confidence weighted interactome and phosphoproteome. For this purpose, we use the Omics Integrator software which solves the prize-collecting Steiner forest (PCSF) problem [2]. On the one hand, it tries to include as many of the proteomic hits as possible; on the other hand, it tries to keep the network small by avoiding using unreliable protein-protein interactions. Using these networks we are able to track enriched biological processes across time points. For example, many biological processes are significantly enriched in any tumors; i.e. apoptosis, cellular response to stress. We are also able to extract the biological processes that are significantly enriched at any time point and in any tumor. Next, we aligned the reconstructed patient-specific networks and identified common and unique pathways across these patients as well as important subnetworks. We also compared these networks based on the functional enrichments to identify the biological processes and pathways that play role in different patients. The results of this study provide us information about the ischemic pathways and proteins besides the cancer related pathways. Because in many studies including TCGA the excision time is not known, the benchmark ischemic pathways and proteins will make us be able to distinguish cancer-related pathways and ischemic artefacts.
Citation Formats
G. Budak, E. Fraenkel, and N. Tunçbağ, “Identification of the Ischemic Pathway Level Changes by Integrating Temporal Phosphoproteome in Ovarian Cancer,” presented at the 5th International Congress ofthe Molecular Biology Association of Turkey (8 - 10 Eylül 2017), İstanbul, Türkiye, 2017, Accessed: 00, 2021. [Online]. Available: