High Performance Computational Systems Biology

Vaclav Stumbauer

HiBi 2009 report

November 2009, Nove Hrady

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Intro
The Microsoft Research - University of Trento Centre for Computational and Systems Biology http://www.cosbi.eu/

http://www.cosbi.eu/hibi09

All the talks and relevant material are attached in the resources directory.

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Overall Summary
Main topics
Parallel stochastic simulation Parallel/distributed model checking Parallel/distributed state space exploration algorithms

Main lessons learnt

Biochemical systems with low numbers of a particular specie -> Stochastic simulation Idea of what different systems biology groups are trying to achieve Lectures and posters brought me to a wide spectra of /at least for me/ novel topics and material Gyus from Brno have a good reputation and relationships with the others, a lot is based on good relationships

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Talk #1 - Mesoscale Modeling of the Bacillus Thuringiensis Sporulation Network Based on Stochastic Kinetics - A. Gonzlez, H. Castro, M. Villamizar et al.
Summary
Bio-pesticides production optimiz (sporulation endotoxines of Bacillus Thuringiensis) Relatively small gene regullatory network SSA - Gillespie simulation of the regullatory network Oportunistic java based grid application

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Talk #1/2 - Gillespie

Gillespie
Relatively old but still heavilly employed stochastic simulation algorithm (SSA) Original scheme is as follows: Single reaction per simulation step Each step 2D PDF function based on reaction rates, reactant populations is calculated Each step is the next reaction and time to that reaction determined based on PDF The original paper is attached - resources/gillespie.pdf

Approximations/dierent variants
-leaping - instead of determining time to the next reaction and one and only reaction to follow, the Tau-Leaping algorithm estimates ocurrence count for each of the possible reactions during the calculated approximate time interval ". Time interval is estimated so that the propensity functions aj (X) "dont change signicantly". Poisson RWs for reactions - the new state vector in each time step is calculated like this: X X(t + ) = X(t) + j Pj (aj (X(t)), )
j
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Talk #2 - Real-time clustering of datasets with hardware embedded neuromorphic neural networks: L. Bako
Neuromorphic means analog/digital VLSI systems that implement models of neural systems and mimic neuro-biological architectures present in the nervous system.

Summary
Spikes based neural net, modied Hebbs rules for learning (modication ->supervised) Hebbs rules basically lead to strenghtening those synapses where both neuorons are ring simultaneously - in general correlated ring of a buch of incoming synapses leads to their strenhtening, uncorrelated to thei weakening Parallel implementation onto FPGA Neural networks based dataset clustering FPGA is a "HW congurable" chip V/HDL is a language for FPGA conguration specication HW implementation was tested by clustering Fisher IRIS dataset Wisconsin breast cancer dataset
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Talk #2 - part 2
O-topic lessons learnt
Swarm Intelligence (SI) - emergent collective behaviour coming from the particular agent simple behavioral rules Articial Immune Systems (AIS) - Immune system mechanisms application to "general" problem solving - applicable e.g. in area of pattern recognition attached documents:
an exhaustive Thesis: resources/Clonal Selection as an Inspiration for Adaptive and Distributed Information Processing.pdf paper on recognition: recources/2_artical_immune_recognition_system.pdf

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Talk #3 - k-PathA (K-shortest PATH Algorithm):A. Ullrich and C.V. Forst

Summary
k shortest paths problem is to list the k paths connecting a given source-destination pair in the graph with minimum total length/weight. Project aims at large biological networks response analysis - as a case study inuenza (H5N1) virus response network in human based model was sought for. Based on MPI/LAM - legacy, Open-MPI is probably the most modern MPI implementation. The paper is full of genetic, proteomic and interaction DB links

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Talk #4 - toolpaper - DiVinE 2.0: High-Performance Model Checking, J. Barnat, L. Brim and P. Rockai
About the authors
The group - The ParaDise labs - comes from Brno. (http://www..muni.cz/paradise/) What may be interesting for us is that they got 6th EU programme 2 grants: ARTIST2 NoE - Testing and Verication Platform EC-MOAN - Scalable Modeling and Analysis Techniques to Study Emergent Cell Behavior http://www.ec-moan.org/

Summary
Parallel/distributed model checking of nite state systems against LTL premises Implementation for multi-core, clusters and CUDA Primarily Computer science relevant - e.g. electronic systems verication Biological networks version under development BEEM - Benchmark for explicit model checkers - maintained by Brno

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Talk #4/2
LTL - Linear Temporal Logic
Logical expressions extended into time. Basic LTL operators: G F X U R must hold true on the whole subsequent path must eventually hold true must hold true at the next state "until" - must hold at least until is true "release" - holds true until is true

An example
An example: Between the time an elevator is called at a oor and the time it opens its doors at that oor, the elevator can arrive at that oor at most twice.

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Talk #5 Stochastic simulations on a grid framework for parallel sweep applications in biological models: E. Mosca, P. Cazzaniga, D. Pescini, I. Merelli, G. Mauri and L. Milanesi.
Summary
Parameter Sweep application - parameter estimation etc. - basically many differently parametrised instances of the system are simulated. Based on -DPP algorithm - multi-volume variant of the -leaping SSA - a combination of a P system and modied -leaping algorithm Parallelised (inherently paralelisable with linear scalability) on Grid (EGEE http://www.eu-egee.org/) Bacterial chemotaxis used as a case study Fitness function based on different chemical species dynamics Quasi-random (low discrepancy) sequences for parameter space sampling Their conclusion ragarding the grid computing :Granularity is important in grid environments because of high failure rates

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Talk #6 Cellular Level Agent Based Modeling On the Graphics Processing Unit - P. Richmond, S. Coakley and D. Romano
Summary

FLAME - FLexible Agent Modelling Environment - formal modelling of agents using the X-Machine X-Machine is basically a nite state machine with the diff that the transitions imply relations X X http://www.amegpu.com/ parallel agent based modelling framework for GPU user just gives agent prescription (combination of XMl an scripted C) Case study - Keratinocyte tissue wound model - Parallel inter-cellular force resolution Different inter - agent messaging schemes are presented Uses rand48 PRNG - I will try this in bioreactor parallel simulation instead of the currently used Mersenne Twister, suppose there might be a performance benet from this
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Talk #7 An ecient GPU implementation for large scale individual-based simulation of collective behavior - U. Erra, B. Frola, V. Scarano and I. Couzin.
Summary
Local behavioral model - emergent collective behaviour Avoidance, attraction, local perception, simple response rules Brute force approach to the proximity problem (local perception) leads to O(n2 ) Uniform grid and GPU based sorting, only individuals from overlapping/adjacent grid cells are considered

School of sh model

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Talk #7/2
Flow control

k-NN search - nd at maximum # k of nearest neighbors in the given radius

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Talk #8 - the search for gene-gene interactions in colorectal cancer: Using HPC to overcome computational barriers - F. Scharinger, F. Reid, P. Graham et al.
Summary
Looking for gene marker colorectal cancer incidence 560,000 gene markers, 1000 cancer patients, 1000 matched controls Rather a tool paper than a regular paper

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Talk #9 Simulation of P Systems with Active Membranes on CUDA - J.M. Cecilia, G.D. Guerrero, J.M. Garca et al.
P Systems
P Systems (Membrane computing) - another form of Natural Computing There are different kinds of P systems, but in general they are comprised of A system of membranes/localised compartments, each containing a multiset of symbols Interaction rules for the symbols Communication rules/membrane transfer rules Membrane rules - dissolution, formation, ... The rules in a P system are applied at random - non-deterministic computation often resulting in multiple solutions The result of a P systems computation - symbols/chemicals present outside of the outermost membrane (when no more reactions may take place).
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Talk #9/2
See resources/Membrane_computing_Intro2004.pdf and resources/membrane_computing_8th_international_conference.pdf for a better idea of P-systems.

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Talk #10 Performance Issues in Evaluating Models and Designing Simulation Algorithms - R. Ewald, J. Himmelspach, M. Jeschke, S. Leye and A. Uhrmacher
While the main topic not that interesting (automatic algorithm and sub-algorithm selection - different SSAs), the paper presents a nice review of different stochastic simulation approaches and relevant literature. The paper is related to the James II OSS modelling and simulation framework - see next slides.

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Talk #11 - The James II framework for modeling and simulation - J. Himmelspach and A. Uhrmacher.
Summary
OSS modeling and simulation framework with many plugins (e.g. different RNG generators etc.) Authors are ambitions - framework is supposed to be a basis for experiment replication http://www.jamesii.org

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Various bits I came over in connection with HiBi

Netlib - www.netlib.org - a collection of mathematical software, papers, and databases.

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