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SYM-9 : Multi-omics



Stuart J. Cordwell
Code / Date
SYM9-1 / March 29 (Fri)
Speaker
Stuart J. Cordwell   CV
Affiliation
The University of Sydney
Title
Multi-omics of the myocardium during ischemia / reperfusion injury
Abstract

Myocardial ischemia / reperfusion (I/R) injury induces profound changes to cellular physiology aimed at improving survival, or leading to cell death if the ischemic period is prolonged. These molecular events are mediated by protein post-translational modifications (PTM) rather than changes in gene and protein expression. We utilised a rodent model of I/R injury to analyse a wide variety of PTMs on a proteomic scale, including phosphorylation-mediated signalling and redox regulation. These data combined have highlighted over 30,000 sites of PTM quantified over a controlled time-course of 1-60 mins ischemia and subsequent reperfusion. Here, we discuss a temporal profile of phosphorylation during ischemia, which shows significant regulation of signalling even within the first 1-2 mins of ischemia, providing targets for functional inhibition that alter myocardial recovery. Additionally, redox modifications of cysteine (Cys) during adaptation to I/R-associated reactive oxygen species (ROS) stress have been profiled and sites of protein damage determined. The functional effects of these protein changes were correlated with a global profile of the myocardial metabolome during I/R. Large-scale and temporal multi-omics offers the potential to identify protective pathways for therapeutic intervention, as well as novel markers of ischemic events.

 

Man Ho Choi
Code / Date
SYM9-2 / March 29 (Fri)
Speaker
Man Ho Choi   CV
Affiliation
KIST
Title
Metabolic signatures of steroids in clinical endocrinology
Abstract

Metabolomics can reveal the states of metabolites within the biological system and provides comprehensive insights by allowing comparisons among different metabolites present in cells, tissues, or organisms. In addition to the biochemical roles of steroid hormones as endocrine messengers, the intracrine pathways have been also identified in steroid-dependent disorders. The exact quantification and qualification of steroids in various biological specimens, such as circulating blood, tissue, hair, and saliva could be the gold standard to elucidate their biochemical actions. Diverse analytical techniques are needed to attain higher coverage of steroid hormones in different biological specimens. Significant advancements have done with mass spectrometry (MS) combined with chromatographic separation methods in the past decades. This presentation provides technical aspects of sample purification techniques for reduction of background noise derived from different sample characteristics using gas and liquid chromatographic methods. The biomedical applications focus on 'state-of-the-art' investigations of metabolic aspects of steroid hormones in different diseases, such as metabolic syndromes and adrenal dysfunctions, which are the most common subjects studied with the help of metabolomics.

 

Min-Sik Kim
Code / Date
SYM9-3 / March 29 (Fri)
Speaker
Min-Sik Kim   CV
Affiliation
Daegu Gyeongbuk Institute of Science and Technology
Title
Multi-Omics analysis of pancreatic ductal adenocarcinomas
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease ranking as the fourth most common cause of cancer-related deaths in the United States. In Korea, the incidence rate for PDAC is only ~3% of all cancer cases, but the relative 5-year survival rate is only ~10%. There are no effective therapies for this cancer that can cure or substantially increase survival and no good diagnostic marker for the disease. Several genetic alterations including KRAS, CDKN2A, TP53, SMAD4 and BRCA2 have been implicated in the pathogenesis of PDAC. A comprehensive exome sequence analysis was recently reportedon a panel of 14 primary PDAC cell lines and 10 xenografts, in which ~1,500 somatic alterations and a core set of 12 signaling pathways activated in PDAC were defined. In addition, recent studies regarding the evolution of PDAC at the genetic level have shown that clonal complexity of metastatic pancreatic cancer is initiated already within primary sites, and organ-specific metastases are derived from different subclones. However, we still do not have a good sense of knowledge about PDAC. In this study, we employed multi-omics technologies to study PDAC at the molecular levels of DNA, RNA, protein and phosphorylation. The result showed the similar landscape of genetic aberrations were observed when compared to TCGA data. Transcriptomic analysis identified subtypes of cancers while proteomic data further revealed detailed sub-groups of PDAC. Interestingly, a few groups of PDAC based on the integrated sub-grouping were segregated from others in that they were sensitive to the current treatment to PDAC. This indicates that the molecule-based markers can be used to find patients who may respond and survive longer and that others who may not respond will have to be treated with other treatment options. Finally, the integration of phosphoproteomic to RNA and proteins data further showed activated pathways of the unresponsive groups that might be new pathways to be targeted to develop novel treatment options for the patients with PDAC.

 

Sureyya Ozcan
Code / Date
SYM9-4 / March 29 (Fri)
Speaker
Sureyya Ozcan   CV
Affiliation
Middle East Technical University
Title
Multiomics-Engaging colors
Abstract

High-throughput omics technologies have revolutionised biological research
by enhancing our understanding of fundamental molecular processes. Despite
the recent advances in evolutionary genomics, human brain development is
still poorly understood. We have combined transcriptomics with four mass
spectrometry (MS)-based omics technologies: proteomics, metallomics,
glycomics and lipidomics, to gain new insights into human brain
development. The integrated multiomics approach was employed to
investigate the human dorsolateral prefrontal cortex (DLPFC) throughout
post-natal development from 69 individuals aged six weeks to 49 years. The
DLPFC is implicated in a variety of complex behaviors and strongly linked to
personality development. High-dimensional data was analyzed using rigorous
statistical methods at different post-natal developmental stages across
multiple omics layers. This integrative multiomics approach reveals novel
insights into the critical stages of cognitive development.

 

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