Network analysis to elucidate natural system dynamics, diversity and performance
Omics-Data has brought into light the fact that nothing is unique in living systems (1). Whatever the scales, the building blocks of life are based on diversity and whatever collective acts they orchestrate, they use many alternative approaches (2).
The diversity lies at the level of individual elements and at the level of their connectivity:
• Chemical information: gene sequences, protein sequences (sequence variants) (3)
• Shape information: cellular morphologies, protein structures, RNAs, DNAs (4)
• Functional dynamics: Molecular dynamics, interactions and thermodynamics
• Collective acts: signaling pathways, metabolisms, protein folding, allostery
Diversity underpins natural system performances bearing robustness and adaptability to perturbations, and supporting rescue and compensatory mechanisms (5). The diversity encompasses notions like combinatorial solutions, alternative solutions and backups and embeds spatial optimization, non-linearity and dynamics. Natural systems also fail and pathologies result from chemical errors (e.g. sequence variants, environmental changes), structural errors, and impaired functions. Thus, just as robustness and adaptability, system failure is born out of diversity and collective responses whose output is negative, at least at some level.
Our challenge is to separate the wheat from the chaff to understand how nature corrects mistakes at the scale of molecular systems, organisms and species. This is the key to natural system resiliency and the rules needed to both design systems inspired by nature and decipher the impact of genetic background on individual disease development and drug responses (6–9).
Essentially the problem is based on individual elements and the layout of their connectivity, which makes network-based models well suited to investigate properties of natural systems (3,10).
Extended deadline for abstract submission for poster presentation and conference registration: April 1st, 2019. A few abstracts will be selected for oral presentations.
1. Gartner, Z. J., Prescher, J. A. & Lavis, L. D. Unraveling cell-to-cell signaling networks with chemical biology. Nat. Chem. Biol. 13, 564 (2017).
2. Smith, J. L., Skiniotis, G. & Sherman, D. H. Architecture of the polyketide synthase module: surprises from electron cryo-microscopy. Curr Opin Struct Biol 31, 9–19 (2015).
3. Laddach, A., Ng, J. C.-F., Chung, S. S. & Fraternali, F. Genetic variants and protein–protein interactions: a multidimensional network-centric view. Curr. Opin. Struct. Biol. 50, 82–90 (2018).
4. Degiacomi, M. T. et al. Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism. Nat. Chem. Biol. 9, 623–629 (2013).
5. Demir, O. et al. Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants. PLoS Comput Biol 7, e1002238 (2011).
6. Rackham, O. J. et al. The evolution and structure prediction of coiled coils across all genomes. J Mol Biol 403, 480–93 (2010).
7. Toyama, B. H. & Hetzer, M. W. Protein homeostasis: live long, won’t prosper. Nat. Rev. Mol. Cell Biol. 14, 55 (2013).
8. Wanieck, K., Fayemi, P.-E., Maranzana, N. & JACOBS, S. Biomimetics and its tools. (2017).
9. Ponzoni, L. & Bahar, I. Structural dynamics is a determinant of the functional significance of missense variants. Proc. Natl. Acad. Sci. 201715896 (2018).
10. Vuillon, L. & Lesieur, C. From local to global changes in proteins: a network view. Curr. Opin. Struct. Biol. 31, 1–8 (2015).
Ivan Junier (Univ. Grenoble Alpes)
Kenneth Knoblauch (SBRI)
Ivan Rivalta (Ecole Normale Superieure Lyon, CNRS)
Anne Siegel (RISA – CNRS)
Laurent Vuillon (Université de Savoie)
Gerhard Stock (Albert Ludwig University, Freiburg)
Matteo Degiacomi (Durham University)
Athi N. Naganathan (Indian Institute of Technology Madras, Chennai)
Michele Caselle (Università di Torino)
Francesca Fanelli (UNIMORE)
Tamiki Komatsuzaki (Hokkaido University)
Takahisa Yamato (Nagoya University)
Franca Fraternali (King’s College London)
David Wales (University of Cambridge)
Pratyush Tiwary (University of Maryland)
Thursday May 2nd 2019 – Day 1
From theory to Experiment
08:30 to 09:00 – Registration
09:00 to 09:30 – Welcome and Introduction
09:30 to 10:30 – David Wales
Energy landscapes: from molecules and nanodevices to machine learning
10:30 to 11:30 – Matteo Degiacomi
Protein integrative modelling using mass spectrometry data
11:30 to 12:30 – Gerhard Stock
Allosteric communication networks
12:30 to 14:00 – Poster Session with cold buffet sandwiches
14:00 to 15:00 – Takahisa Yamato
Energy Transport Networks of Residue-Residue Interactions in Proteins
15:00 to 16:00 – Laurent Vuillon
Discrete mathematics for protein structures
16:00 to 16:30 – Coffee Break
16:30 to 18:00 – Presentation
19:00 to 23:00 – Social Dinner
Friday May 3rd 2019 – Day 2
Diversity-Multi-scales- Robustness and fragility
09:00 to 10:00 – Kenneth Knoblauch
Hierarchical relations in the cortical graph
10:00 to 11:00 – Ivan Junier
Genome tinkering and the shaping of regulatory networks
11:00 to 12:00 – Michele Caselle
Using network theory to identify cancer drivers genes
12:00 to 13:30 – Poster Session with cold buffet sandwiches
13:30 to 14:30 – Franca Fraternali
Mutations and Variations in Health and Disease: Protein Interaction Networks and their Multiscale Interpretation
14:30 to 15:30 – Anne Siegel
Exploring metabolism diversity with reasoning-based methods
15:30 to 16:30 – Presentation
16:30 to 18:30 – Discussion
Saturday May 4th 2019 – Day 3
Protein structure and dynamics and relation to function
09:00 to 10:00 – Francesca Fanelli
Uncovering Protein Function by Structure Network Analysis
10:00 to 11:00 – Athi N. Naganathan
Insights into Long-Distance Energetic Coupling in Proteins via Mutational Perturbations
11:00 to 12:00 – Ivan Rivalta
Tracking allosteric signals with community network analysis of protein motions
12:00 to 13:00 – Lunch
13:00 to 14:00 – Tamiki Komatsuzaki
Deciphering hierarchical features in reaction network and energy landscape
14:00 to 15:00 – Pratyush Tiwary
Three birds with one stone: Reaction coordinate, thermodynamics, and kinetics from allatom simulations
15:00 to 17:00 – Presentation
17:00 to 17:30 – Closing Word