Human Quantitative Dynamics Workshop

December 1 & 2, 2015

Bethesda MD

Human Quantitative Dynamics Workshop

9-14-2015 - Final

Bethesda Hyatt Regency, Bethesda MD

December 1 2015

Session 1 Overview : Why do we need quantitative dynamics?

9:00 am - An initial overview of HQD - Integrating Big Science and R01/R21
Ravi Iyengar - Icahn School of Medicine at Mount Sinai

9:20 am - What can HQD for Basic Research focused on understanding complex multi-scale biology like tissue and organ development and physiology/homeostasis
Marian Walhout - University of Massachusetts Medical School

9:40 am - What can HQD do for Precision Medicine
Garret FitzGerald - University of Pennsylvania

Session 2 What sort of measurements do we need to fully understand quantitative dynamics ?

10:15 am - The Human Proteome Atlas
Mathias Uhlen Royal Institute of Technology (KTH)

10:35 am - Analysis of network perturbations in human disease
Marc Vidal - Harvard Medical School

10:55 am - The protein database landscape: Achievements and limitations
Rolf Apweiler - EMBL-EBI Wellcome Trust

11:15 am - Crowdsourcing approaches for parameter estimation and building whole cell models
Gustavo Stolovitzky - IBM Research

11.35 am - Formatting the Open Discussion - This session will be focused on developing questions and structure for after lunch Open- Structured-Discussion
Brenda Andrews - University of Toronto

12:45 pm – 1:30 pm - Brenda Andrews

1. Will HQD, if successful, be useful for biomedical sciences? What would be the benchmarks for success?

2. Proteins, metabolites, and interactions in a specific cell type: how complete is complete?

3. There is very little incentive to perform high throughput biochemical studies now. How do we encourage high throughput technology development in biochemistry and cell biology to study dynamics?

Session 3 Successes and failures of large-scale projects: what can we learn to design new projects

1.30 pm - Overview
Sarah Dunsmore - NIGMS

1.40 pm - Multiomics projects for precision medicine: Dynamic analysis of healthy and disease states using personal omics profiling
Mike Snyder - Stanford University

2:00 pm - Studying genetic interaction networks
Brenda Andrews - University of Toronto

2.20 pm - The design of the BRAIN Project
Andrea Beckel –Mitchener - NIMH

2:40 pm - GTEx: Successes and challenges
Kristin Ardlie - Broad Institute

3:00 pm - Defining scope of big projects to enable success
Ajay Pillai - NHGRI

Session 4 Measuring Protein – Protein Interactions - Complexes and Kinetics

3:40 pm - Proteomic approaches to identify protein-protein interactions and protein complexes
Ann Claude Gingras - Mount Sinai Hospital

4:00 pm - Towards affinity quantification of protein-protein interactomes?
Gilles Travé - École Supérieure de Biotechnologie de Strasbourg

4:20 pm - Measuring protein–ligand interactions
Anne-Claude Gavin - EMBL-Heidelberg

4:40 pm - Quantitative profiling of protein-protein and drug-target interactions in human cells
Mikko Taipale - University of Toronto

5:00 pm - New technologies to study cellular quantitative dynamics
Marc Birtwistle - Icahn School of Medicine at Mount Sinai

5:20 pm - Systematizing the analysis and assembly of executable models
Peter Sorger - Harvard Medical School

5:40 pm – 6:20 pm - Salvatore Sechi,

Discussants: Mikko Taipale, Peter Sorger, Marc Birtwistle

1. What additional experimental technologies do we need to increase throughput?

2. Can we assess what is commercially available and determine how it might fit in?

3. How do we start thinking about QA/QC issues early on? Is technology the major bottleneck, or do we have to change how we deal with QA/QC?

4. How do we identify and classify metadata associated with different experimental technologies?


December 2

Session 5: Computable Databases for Human protein-protein interactome

9:00 am - Data Integration in a cell type selective manner
Olga Trayanoskaya - Princeton University

9:20 am - Capturing dynamics from multiple data sets to identify rules that govern signal processing from complex input
Michael J. Lee - University of Massachusetts

9:40 am - Data curation and database resources to enable quantitative systems biology
Ravi Iyengar - Icahn School of Medicine at Mount Sinai and Olga Troyanoskaya - Princeton University (in place of Kara Dolinski)

10:00 am – 10:45 am - Olga Troyanskaya

Discussants: Marc Vidal, Shankar Subramaniam

1. How do we resolve qualitative vs. quantitative features of databases?

2. How do we annotate common and distinct features of data for different cell types?

3. Associating metadata and QA/QC with core HQD data

10:15 am - Structured Open Discussion Olga Trayanoskaya, Marc Vidal

Session 6 Measuring Small Molecule Cellular Entities

11:00 am - One-hour proteomes and deep sequencing
Joshua Coon - University of Wisconsin

11:20 am - Metabolomics to study enzymatic activity on a genome-wide scale
Theresa Fan - University of Kentucky

11:40 am - Quantitative profiling of lipid metabolities
Robert Murphy - University of Colorado

Session 7 Integrating Informatics with Modeling Tools

1:40 pm - Integrative Informatics for cellular metabolites and macromolecules
Shankar Subramaniam - University of California

2:00 pm - Modeling approaches for whole cell dynamics: Challenges and opportunities
Chad Myers - University of Minnesota

2:00 pm - Modeling and analysis tools for whole cell modeling
Les Loew - University of Connecticut

2:20 pm – 2:40 pm - Les Loew

Discussants: Theresa Fan, Anne-Claude Gingras, Bob Murphy, Mathias Ulhen, Joshua Coon

1. Can we use metabolite dynamics to infer enzyme activities and calculate Kms?

2. What about measuring post-translational modifications?

3. Do we need to explicitly measure enzymatic activities? Can we generate canonical guidelines for parameter assignment?

Discussants: Chad Meyers, Olga Troyanskaya, Shankar Subramaniam

4 Data structure for statistical and graph theory models

5. Data structure for ODE models

6. How about other types of dynamical models, e.g., agent based models?

Session 8 Contours of Pilot Projects

3:00 pm - A C. Elegans pilot project
A.J. Marian Walhout - University of Massachusetts

3:20 pm - Multiscale modeling: Understanding adaptive immune responses in terms of dynamic molecular networks within each cell
Alexander Hoffmann - UCLA

3:40 pm - A human iPSC-derived cardiomyocytes cell project - all it takes to make & keep a beat
Ravi Iyengar - Icahn School of Medicine at Mount Sinai

4:00 pm – 5:00 pm Sarah Dunsmore & Marian Walhout

Discussion: Olga Troyanskaya, Alex Hoffmann, Ravi Iyengar, Ajay Pillai, Salvator Sechi, David Balshaw

1. Reproducibility and applicability in differing contexts: Structuring large-scale projects for success, defining and constraining scope

2. Community engagement and how big projects can enable small projects

3. Path forward engaging various interested parties

4. Outline for Workshop Report