October 2014 Meeting; Madrid, Spain

 

Cancer I: 8:00 – 9:20 am. Monday October 6th, 2014

Organizers: Hui Zhang, Christopher Kinsinger, and Edouard Nice

Room D

 

Chair/Modulator: Hui Zhang

 

8:00 - 8:10 am Hui Zhang: Overview of Ca-B/D-HPP

 

8:10 - 8:25 am Ruedi Aebersold: Quantifying cancer related proteins via targeting MS assay resources

 

8:25 - 8:40 am Christopher Kinsinger: The CPTAC Initiative

 

8:40 – 8:55 am Robert Moritz: MRM

 

8:55 – 9:10 am Edouard Nice: Towards the Human Proteome: Analysis of Alternative Clinical Samples

 

9:10 – 9:20 am Open discussion

  

 

Cancer II: 8:00 – 9:20 am. Tuesday October 7th, 2014

Organizers: Hui Zhang, Christopher Kinsinger, and Edouard Nice

Room D

 

Chair/Modulator: Jacob Kagan

 

Discussion Panel:  Bill Hancock, Bryan Krastins, Christopher Kinsinger, Connie Jimenez, Daniel Chan, Edouard Nice, Henry Rodriguez, Hui Zhang, Jacob Kagan, Jashua Labaer, Josip Blender, Mark Baker, Peter James, Robert Moritz, Ruedi Aebersold, Shoba Ranganathan, Sam Hanash, Zhen Zhang

 

Key Discussion Points

 

• Mining the existing datasets and database

• Dissemination of data and resources: generation and/or linking of appropriate websites

• Generation of a directory of key players, skills, cancer targets, and available assays

• Key persons to take responsibilities

• Prioritization of targets in the top 5 cancers

• Use of animal models

• Understand the normal/personalized medicine

 

 

September 2013 Meeting; Yokohama

 

Date/Time: Monday, September 16, 2013, 08:15 - 09:30 (meeting room TBD)

 

 

Workshop Title: Cancer

 

 

Organizer(s): Hui Zhang

Center for Biomarker Discovery and Translation, Department of Pathology, Johns Hopkins University, USA

 

Juan Pablo Albar

CEI-UAM+CSIC Proteomics Platform, Spain

 

 

Rapporteur Name/Email:

Christopher Kinsinger [kinsingc@mail.nih.gov]

Session Overview Abstract to describe your initiative (broadly) and the session - 250 words max.  

 

Featured speakers can be listed, the format (speakers, panel, open discussion, etc)

 

If you have speakers you can also indicate timing of talks in this section.

The Cancer-HPP attempts to generate and disseminate the assays and resources to support the analysis of biological networks underlying biological processes and cancer. The use of emerging mass spectrometry (MS)-based platforms such as selected reaction monitoring (SRM) or targeted data extraction for candidate proteins from SWATH MS data has become an increasingly popular method for quantitative analysis of target proteins. It has been shown that the use of synthetic peptide standards and isotope dilution makes identification and accurate quantitation of proteins in a multiple laboratories possible. Therefore, the assays, once developed, can be easily transferred and used in other laboratories. Acceptance of high throughput MS assays for proteins or protein modifications has been limited due to the difficulty in establishing assays and the availability of the assays comparing to using traditional antibody based assays, here we propose an international effort to target cancer proteins in each cancer type. By working together, we can create a synergistic effort to work with a list of cancer protein targets, develop assays, and make assays available. We further discuss the procedure to accrue a list of target proteins from each cancer type, the strategy for assay development, quality control, and procedure and materials needed for transferring the established assays to a new laboratory.  

SPEAKERS

Speaker 1

Name, Affiliation: Christopher Kinsinger

Clinical Proteomic Tumor Analysis Consortium (CPTAC), National Cancer Institute, USA

Speaker 1 

Title or Topic Area

CPTAC - a Proteogenomics Network for Cancer

Speaker 1 Abstract

Molecular characterization of human cancers has generated large volumes of genomic data through comprehensive and coordinated efforts such as The Cancer Genome Atlas (TCGA) project. However, the mechanisms by which cancer genes singly or cooperatively transform cells remain poorly understood. Proteomic characterization of cancer tissues with genomic data represents a key step in not only verifying the genomic alterations at the protein level, but also allowing for the analysis of unique features that are inherent to proteins including post-translational modifications.  The proteomic characterization of cancer tissues is therefore essential for the development of a successful strategy to reduce cancer mortality. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) was launched by the National Cancer Institute (NCI) as a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of robust and quantitative proteomic technologies and workflows. CPTAC aims to systematically identify proteins that derive from alterations in cancer genomes and related biological processes, and provides this data with accompanying assays and protocols to the public. In this initiative session for the Cancer Proteome-Human Proteome Project (CP-HPP), we will describe the specimens, proteomic technologies, workflows, and public data releases of the CPTAC program.

 

 

Speaker 2

Name, Affiliation

Guo Tiannan

ETH Zurich, Institute of Molecular Systems Biology, Switzerland 

Speaker 2

Title or Topic Area

Analysis of Tissue Biopsies by PCT-SWATH

Speaker 2 Abstract

Fast, quantitatively accurate, deep and reproducible proteomic analysis of complex biological samples remains a major hurdle in systems biology and systems medicine. Here we propose a method to convert the proteome contained in small (biopsy) cell or tissue sample into a digital data set that contains signature fragment ion patterns for all peptides derived from the sample. These datasets can be then perpetually mined in silico. In essence, the method converts the physical proteome in a (clinical) sample into a permanent digital representation. The method is built on pressure-cycling technology and SWATH-MS. The entire workflow can be completed within 12 hours. Subsequent targeted data analysis offers unprecedented performance in identifying and quantifying low-abundance signaling protein networks in human tissues in an extendable manner. We have applied this method to a kidney cancer cohort, and uncovered dis-regulated signaling protein networks.

 

 

Speaker 3

Name, Affiliation

Edouard Nice

Clinical Biomarker Discovery and Validation, Monash Antibody Technologies Facility, Monash University, Australia

Speaker 3

Title or Topic Area

Proteomics-Based Studies on Colorectal Cancer

Speaker 3 Abstract

Colorectal cancer (CRC) is currently the third most common cause of cancer death worldwide. If detected early while the disease is localised, 5 year survival following simple surgical resection is greater than 90%. By contract, if the cancer has metastasised, 5 year survival is less than 10%. Improved early detection and understanding of the metastatic process is clearly urgently required. 

In this presentation I will describe some of our recent proteomics-based studies to both identify novel faecal biomarkers for detection and surveillance of the disease and also describe how we have we have integrated shotgun proteomics approach with a genome-wide transcriptomic approach (RNA-Seq) on a set of human colon cancer cell lines (LIM1215, LIM1899 and LIM2405) to both identify cancer associated proteins with differential expression patterns as well as protein networks and pathways which appear to be deregulated in these cell lines.

 

 

Speaker 4

Name, Affiliation

Zhen Zhang 

Biomarker Discovery and Translation, Johns Hopkins University, USA

Speaker 4

Title or Topic Area

Integrative Analysis - Bridging the Gaps in Genetic Information Flow between Genomic and Proteomic Data

Speaker 4 Abstract

Molecular characterization of human cancers has generated large volumes of genomic and proteomic data through comprehensive and coordinated efforts such as TCGA and CPTAC. However, analyses of such genomic and proteomic data, even when comparing the same phenotypic differences, often yield results that do not overlap much in terms of the corresponding genes. We will present our effort in developing an integrative analysis approach and associated bioinformatics tools to take advantage of existing knowledge and databases such as pathways and interactomes, to search for the missing layer of molecular entities that could provide the most plausible linkage between the observed phenotype-dependent genomic alterations and proteomic expression changes. Results from such tools will not only provide plausible interpretations of the analysis results but also generate meaningful hypotheses for further verification. 

Speaker 5

Name, Affiliation

Peter James

Department of Immunotechnology, Lund University, Sweden

Speaker 5

Title or Topic Area

Breast Cell Index and Atlas Projects

Speaker 5 Abstract

We have analysed over 450 primary human breast tumours and seven cells lines that represent the most common types of breast cells. These include model human cell lines representing the main molecular portraits of breast cancer as defined by mRNA expression (Luminal A and B, Basal, ErbB2, and normal-like) as well as a breast adipocyte and fibroblast cell line. In addition to cataloguing protein expression levels and modifications, we have been examining the intracellular distribution of proteins amongst the organelles. We have built up a large spectral library that enables us to create and validate rapid SRM assays for various aspects of breast cancer development and therapy choice and response monitoring. For example we have developed SRM assays for the majority of the proteins involved in DNA repair to allow monitoring of patient response to chemo- and radiotherapy. SRM analysis also allows a rapid determination of the levels of the hormone receptors (Estrogen, Progesterone and HER receptors) as well as known proteins involved in therapy resistance. We have been analysing the changes in protein expression during cancer advance using paired sets of primary tumour and local recurrence and comparing this to primary tumour and distal metastasis. This will enable us to more accurately define the degree of aggressiveness of a tumour and to develop a method to test for the presence of cancer cells in the margins of the primary tumour and in the sentinel node.

Speaker 6

Name, Affiliation

Dong Li and Fuchu He

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences, National Engineering Research Center for Protein Drugs, China.

Speaker 6

Title or Topic Area

Human Proteome Knowledge Discovery Gateway：Progress and Perspective

Speaker 6 Abstract

High-throughput proteomic research approaches, such as mass spectrometry and antibody-based experiments, have generated a great amount of heterogeneous datasets. Mining knowledge from these datasets presents significant challenges, including the quality control, storing, processing, integrating and visualization of various types of proteomic data.

 

To address these challenges, we are constructing a human proteome knowledge discovery gateway. First, an interactive, configurable and extensible, configurable and interactive workflow-based platform will be constructed to analyze the proteome datasets based on the open-source galaxy framework on a cloud infrastructure. And now, this platform has integrated the analyses tools for identifying missing proteins, mapping peptides onto chromosomes, integrating peptide with ENCODE datasets, protein annotation, Gene Ontology enrichment analyses, protein biological network/pathway analyses, fundamental statistical analyses and machine learning. More importantly, this platform also integrates a configurable workflow system to combine these software tools, supporting workflow construction, editing, running,  sharing and viewing. Second, bioinformatics browsers will be integrated into this gateway including the chromosome-based proteome browser (CAPER) and pathway-based proteome browser (PAPER). And now CAPER has been available online as a web-based, user-friendly web service, which can display proteomic data sets and related annotations comprehensively, CAPER employs two distinct visualization strategies: track-view for the sequence/site information and the correspondence between proteome, transcriptome, genome, and chromosome and heatmap-view for the qualitative and quantitative functional annotations. The PAPER will assign the proteome datasets to the human biological pathways, and this service will be online as soon as possible. Third, application software will be developed to annotate the human genome, such as finding novel protein-coding genes and presenting the correlation between the chromosome to genes, epigenome, proteomes, and phenotype, and also to find the key regulatory molecules/modules, the potential drug target and biomarkers by mapping proteome profile to human pathways. 

 

Taken together, the human proteome knowledge discovery gateway will greatly facilitate the complete annotation and functional interpretation of the human genome by proteomic approaches, thereby making a significant contribution to the Human Proteome Project and even the human physiology/pathology research.

Panel Discussion

 

Panel 1

Name, Affiliation

Hisashi Narimatsu

Glycogene Function Team, Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Open Space laboratory (OSL), Japan.

Panel 2

Name, Affiliation

Tadashi Kondo 

Division of Pharmacoproteomics, National Cancer Center Research Institute, Japan.

Panel 3

Name, Affiliation

Sam Hanash 

Clinical Cancer Prevention-Research, Red & Charline McCombs Institute for the Early Detection and Treatment of Cancer, 

The University of Texas MD Anderson Cancer Center, USA

Panel 4

Name, Affiliation

Leigh Anderson 

SISCAPA Assay Technologies, Inc, USA

Panel 5

Name, Affiliation

Ignacio Casal

ProteoRed-ISCIII, CIB-CSIC, Spain 

 

2012 Meeting; Boston, USA

 

Room 311, Level 3

Leadership: Hui Zhang

WInD 7:30 - 8:15 am Proteomics Technologies, Workflow, and Data Release Related to CPTAC Program; Hui Zhang1; Christopher Kinsinger2; 1Johns Hopkins University, Baltimore, MD; 2The Clinical Proteomic Tumor

Analysis Consortium, National Cancer Institute, National Institutes of Health.

 

7:30 – 7:50 am Clinical Proteomic Tumor Analysis Consortium, A Human Cancer Proteome Project; Christopher Kinsinger; National Cancer Institute, Bethesda, Maryland.

7:50 – 8:05 am Comprehensive Analysis of Proteins and Protein Modifications: Changes beyond Protein Expression; Hui Zhang; Johns Hopkins University, Baltimore, Maryland.              

8:05 – 8:20 am The Vanderbilt Proteome Characterization Center; Robbert Slebos; Vanderbilt University Medical Center, Nashville, Tennessee.

8:20 – 8:35 am Profiling PTM Dynamics Using the Human Proteome Microarrays; Heng Zhu; Johns Hopkins University, Baltimore, Maryland.

8:35 - 8:45 am Open Discussion: How CPTAC and Other Cancer Related Proteomic Data Could Flow into the HUPO-HPP.