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SYM-10 : Proteogenomics



Shinya Ohta
Code / Date
SYM10-1 / March 29 (Fri)
Speaker
Shinya Ohta   CV
Affiliation
Kochi University
Title
Proteomics analysis of mitotic chromosomes with using nano Random Forest
Abstract

Packaging of DNA into condensed chromosomes during mitosis is essential for the faithful segregation of the genome into daughter nuclei. Although studied for over 100 years, mitotic chromosome structure and protein network are yet to be fully elucidated. Here, we used stable isotope labeling with amino acids in cell culture (SILAC) to compare the proteomes of mitotic chromosomes isolated from cell lines harboring conditional knockouts of members of the condensin (SMC2, CAP-H, CAP-D3), cohesin (Scc1/Rad21), and SMC5/6 (SMC5) complexes. Our analysis revealed that these complexes associate with chromosomes independently of each other, with the SMC5/6 complex showing no significant dependence on any other chromosomal proteins during mitosis. To identify subtle relationships between chromosomal proteins, we employed a nano Random Forest (NRF) approach to detect protein complexes and the relationships between them. Our NRF results suggested that as few as 113 of 5,058 detected chromosomal proteins are functionally linked to chromosome structure and segregation. Furthermore, NRF data revealed 23 proteins that were not previously suspected to have functional interactions with complexes playing important roles in mitosis. Subsequent small-interfering-RNA-based validation and localization tracking by green fluorescent protein-tagging highlighted novel candidates that might play significant roles in mitotic progression. To test the power of proteomics approach for mitotic chromosomal structre, we considered a classical model for mitotic chromosome formation proposes that non-histone proteins act as a structural framework called the chromosome scaffold. We identified entire chromosome scaffold components with thses series of quantitative proteomics. Actually, the fusion protein of BAZ1B/WSTF (Williams Syndrome Transcription Factor), that was one of most enriched protein in scaffold fraction, localized mitotic chromosome axis. Knocking BAZ1B and its homologue BAZ1A out has caused mitotic progression error. And its double knock-out cells showed aberrant timing of chromosome condensation in prophase. Therefore we propose that the BAZ1A and BAZ1B might has roles in the chromosome scaffold for construction of mitotic chromosome condensation in early mitosis.

 

Dongwan Hong
Code / Date
SYM10-2 / March 29 (Fri)
Speaker
Dongwan Hong   CV
Affiliation
National Cancer Center
Title
Proteogenomic data sharing of National Cancer Center Korea
Abstract

Since the 2016 Korea-U.S.-Japan public health ministerial summit and the 2017 meeting among the official representatives, National Cancer Center (NCC) Korea, the U.S National Cancer Institute, and National Cancer Center of Japan have increased their efforts to collaborate on cancer research and to enable transnational data sharing. For this partnership, Korea has decided to concentrate its research efforts on unraveling proteogenomics in the context of tumorigenesis, and has been actively studying incurable cancers and childhood cancers. In particular, Korea is currently developing a data sharing system that integrates proteogenomic and clinical data while complying with international standards. Multi-omics data repositories for commonly diagnosed cancers among Koreans, incurable cancers, and childhood cancers lack statistical power at the individual hospital level. We therefore recognize that samples should be shared at the national level. Korea plans to increase national sample-sharing efforts starting from the regional cancer centers. The representatives convened at the 2017 trilateral meeting decided that the U.S National Cancer Institute and National Cancer Center of Japan will each contribute at least 300 to 400 proteogenomic data. They also agreed that data storage and transfer should satisfy the guidelines set by the International Standard Organization (ISO). At NCC Korea, as a stepping stone towards the realization of precision oncology, we have doubled our efforts to establish research networks both domestically and internationally. We have also reached out to various stakeholders of this vision in order to form a strategic alliance. These stakeholders include the Korean Liver Cancer Association, Korean Society of Coloproctology, Korean Urological Oncology Society, Korean Society of Cancer Prevention, Korean Cancer Association, Korean Cancer Society, Korean Breast Cancer Society, and regional cancer centers in Korea. Notably, we are currently coordinating with the Ministry of Health and Welfare, Ministry of Science, ICT and Future Planning, and Ministry of Strategy and Finance to create a cancer registry that can readily integrate and leverage clinical, genomic, and imaging data as well as research findings at bedsides across the nation. To date, we have generated proteomic and genetic (proteogenomic) profiles for over 3,000 patients and are annually adding around 1,000 proteogenomic samples. We are also pooling detailed patient data on specific malignancies such as pediatric, gastric, prostate, lung, breast and rare cancers through our alliance network with hospitals nationwide. Following the 2017 meeting, NCC Korea delegated its bioinformatics analysis team to develop a transnational data-sharing system for their proteogenomic data in collaboration with the US National Cancer Institute. The data from this undertaking will be shared through the International Cancer Genome Consortium’s ARGO project, for which NCC is a regional data-processing center. Finally, we are developing a proteogenomics database, ARCHON (Advanced poRtal of Clinical History and multi-Omics iNformation). ARCHON will set the stage for standardization of nationwide clinical proteogenomic data and will provide various analysis toolkits.

 

Sang Myung Woo
Code / Date
SYM10-3 / March 29 (Fri)
Speaker
Sang Myung Woo   CV
Affiliation
National Cancer Center
Title
Proteogenomics: the path to precision medicine in cholangiocarcinoma
Abstract

The biliary tract or the biliary drainage system includes the intra- and extrahepatic bile ducts and the gallbladder. The term cholangiocarcinoma (CC) refers to all tumors arising from bile duct epithelium. CCs are characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. This leads to a paucity of data from which to define the natural history and optimal treatment regimens. Overall, these are highly lethal cancers with a few reported long-term survivors.1
While CC is generally rare in Western countries1,2, it is more common in Korea, with an estimate of 3500 cases diagnosed annually2. Currently, surgical resection remains the only potentially curative treatment, but many patients develop recurrence. Thus, effective postoperative adjuvant therapy is required to prolong survival in CC patients undergoing surgery. However, no standard postoperative treatment has been established yet. Even once established the gemcitabine plus cisplatin combination as the current standard of care for first line systemic therapy3, the prognosis of patients with CC has remained dismal.
CC is rare in terms of devoted studies, with a series of questions about pathogenesis, diagnosis and treatment left unanswered4. In contrast with other cancer types, such as breast, lung and colorectal, the road towards a precision medicine in CC is much more bumpy because of the wide heterogeneity of the tumor and the uncertainties on the genomic profile. Many clinical trials based on genomic and transcriptiomic information are still struggling because of lack of knowledge about actionable targets. Recent proteogenomic studies in human ovarian, breast, colon, and rectal cancers revealed a relatively low degree of concordance between the mRNA and protein expression, underlining that proteomics may unveil important biological processes involved in tumorigenesis5. Here, we are going to introduce the NCC-KBSI project regarding an integrative multi-omics approach to precision medicine of CC.

 

Feng Ge
Code / Date
SYM10-4 / March 29 (Fri)
Speaker
Feng Ge   CV
Affiliation
University of Chinese Academy of Sciences
Title
Proteogenomic Analysis of a Model Diatom
Abstract

Diatoms comprise a diverse and ecologically important group of eukaryotic phytoplankton that significantly contributes to marine primary production and global carbon cycling. Phaeodactylum tricornutum is commonly used as a model organism for studying diatom biology. Although its genome was sequenced in 2008, a high quality genome annotation has still not been obtained for this diatom. Here we develop a systematic approach for conducting an integrated proteogenomic analysis of P. tricornutum using mass spectrometry (MS) based proteomics data. Our proteogenomic analysis unambiguously identifies close to 8300 genes and reveals 606 novel proteins, 506 revised genes, 94 splice variants, 58 single amino acid variants, and a holistic view of posttranslational modifications in P. tricornutum. We experimentally confirm a subset of novel events and provide MS-evidence for more than 200 micropeptides in P. tricornutum. These findings expand the genomic landscapes of P. tricornutum and provide a rich resource for the study of diatom biology. The proteogenomic pipeline we developed in this study is applicable to any sequenced eukaryotes and so represents a significant contribution to the toolset for eukaryotic proteogenomic analysis. The pipeline and its source code are freely available at https://sourceforge.net/projects/gapeproteogenomic.

 

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