Open worm public hangout 10-08-11

What I cannot create I do not understand Richard Feynman’s last board

A multi-scale data problem Scale Whole brain data (20 um microscopic MRI) Mosiac LM images (1 GB+) Conventional LM images Individual cell morphologies EM volumes & reconstructions Solved molecular structures

Reverse-engineering? A system whose mechanisms are obscured

What is reverse-engineering? System whose mechanisms are obscured Individual components and an explanation of how they fit together

What is reverse-engineering? Provide a framework of parts ready to be snapped together

Put the parts back together

A multi-scale synthesis problem

Simulation-based research
Challenging intuition via predictive models
Construction of models requires deep organization of understanding of a system
Forces you to fill in gaps
Observing unexpected behaviors produced by the models
Able to look across multiple variables at the same time
Can do experiments that would otherwise be impossible to do in a real biological system

Enter the worm: c. elegans What’s up, baby?

Virtual physical organisms in a computer simulation

In search of nature’s design principles via simulation
How can a humble worm regulate itself?
Reproduces
Avoids predators
Survives in different chemical and temperature environments
Seeks and finds food sources in an ever changing landscape
Distributes nutrients across its own cells
Manages waste and eliminates it
If we can’t understand genes to behavior here, why would we expect to understand it anywhere?

Enter the worm: c. elegans I’ve only got 1000 cells in my whole body… please simulate me!

A complete simulation of the worm’s brain, body and environment Simulated World Detailed simulation of worm body Detailed simulation of cellular activity

The goal: understanding a faithfully simulated organism end to end Extracting mathematical principles from biological systems is necessary if we are going to understand and reconstruct the much larger system of the human.

Outreach: put the model online and let the world play with it
Sex: Hermaphrodite
Interested in: Escaping my worm Matrix
Relationship status: Its complicated.

Worm biology
~1000 cells / 95 muscles
Neuroscience:
302 neurons
15k synapses
Shares cellular and molecular structures with higher organisms
Membrane bound organelles;
DNA complexed into chromatin and organized into discreet chromosomes
Control pathways
Genome size: (9.7 x 10 7 base pairs or 97 Megabases), vs human: 3 billion base pairs (3 X 10 9 bp or 3000 Megabases).
C. elegans homologues identified for 60-80% of human genes (Kaletta & Hangartner, 2006)

C. Elegans disease models Kaletta & Hengartner, 2006

Can present drugs Kaletta & Hengartner, 2006

Entire cell lineage mapped

Full connectome Varshney, Chen, Paniaqua, Hall and Chklovskii, 2011

P. Sauvage et al. / Journal of Biomechanics 2011 Biomechanics

Interrogation of Behavior

Core platform: Open Worm project

One core hooks together multiple simulation engines addressing diverse biological behavior

Estimates of computational complexity
Mechanical model
~5 Tflops
Muscle / Neuronal conductance model
~240 Gflops
One Amazon GPU cluster provides 2 Tflops
Source: http://csgillespie.wordpress.com/2011/01/25/cpu-and-gpu-trends-over-time/

Mechanical model Palayanov, Khayrulin, Dibert (submitted)

3D body plan Christian Grove, Wormbase

Team – A brief history

Collaboration technologies used

Jan – Sept 2011

Architecture

Neuronal model GPU Performance Testing: 302 Hodgkin-Huxley neurons for 140 ms (dt = 0.01ms) Architecture proof of concept using Hodgkin-Huxley neurons ms

Worm Browser http://www.youtube.com/watch?v=nAd9rMey- _0

Physics: SPH Smoothed particle hydrodynamics (SPH) algorithm for soft-body / liquid finite element interactions

Soft-body & fluid mechanics

Finite element modeling

C.elegans neuron models in NeuroML

Mendeley group has 234 references

Presented poster at Neuroinformatics 2011

OpenWorm links:
Project page: http ://code.google.com/p/openworm /
Twitter: @openworm
Mailing List: http://groups.google.com/group/ openworm

Sept 2011 – March 2012

Muscle cell with “arms” Cell Body 5 arms, 10 compartments each, passive currents Cell body, 1 compartment, active currents Boyle & Cohen, 2007

Case study: locomotion Gao et al, 2011

Conductance model of c. elegans muscle cell Boyle & Cohen, 2007

Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Quadrant 1 Quadrant 2 Quadrants of muscle cells

Genetic Algorithms and Parameter optimization Achard, De Schutter, 2006

Gaming and crowdfunding

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Open worm public hangout 10-08-11

by Stephen Larson

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