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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements Topological Data Analysis Applied to Idiotypic Network Matteo Rucco 1 F. Castiglione 2 , E. Merelli 1 [email protected] 1 University of Camerino - 2 Institute for Computing Applications (IAC) ”M. Picone” February 25, 2015
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Page 1: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

Topological Data Analysis Applied toIdiotypic Network

Matteo Rucco1

F. Castiglione2, E. Merelli 1

[email protected]

1University of Camerino - 2Institute for Computing Applications (IAC) ”M. Picone”

February 25, 2015

Page 2: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

OUTLINE

Theoretical introductionTopological data analysisClique Weight Rank Persistent Homology (CWRPH)

Experiment: Topological Data Analysis of Idiotypic NetworkIdiotypic networkSimulationPersistent EntropyTopological-holes analysis: communities detection

Conclusions

Page 3: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

TOPDRIM - TOPOLOGY DRIVEN METHODS FOR

COMPLEX SYSTEMS

The goal of this project is to providemethods driven by the topology of datafor describing the dynamics of multi-levelcomplex systems

http://www.topdrim.eu

Page 4: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

TOPOLOGICAL DATA ANALYSIS FOR STUDYING

COMPLEX SYSTEMS

Topological Data Analysis (TDA) is a subarea of computationaltopology that develops topological techniques for robustanalysis of scientific data: point cloud and complex networks.

I In Petri et al. (2014),topological methods havebeen applied forunderstanding the effect ofpsilocybin.

I In Reidys et al. (2011),topological methods havebeen used for predicting RNApseudoknots

Page 5: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

SIMPLICIAL COMPLEXA topological space is generated by simplicies (a convex hull ofk+1 vertices):

A nested collection of simplices is a simplicial complexMore formally: a simplicial complex K on a finite setV = {v1, v2, . . . , vn} of vertices is a non-empty subset of the powerset of V, so that the simplicial complex K is closed under the formationof subsets

Left: a simplicial complex. Right: a collection of simplices but that is not asimplicial complex.

Page 6: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

HOW TO BUILT A SIMPLICIAL COMPLEX

Vietoris-Rips, Witness, Neighborhood, Clique-complexes

Left: example of Vietoris-Rips. Right: example of landscape analysis

Page 7: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

PERSISTENT HOMOLOGY - FILTRATION

The basic aim of persistent homology is to measure the lifetime ofcertain topological properties of a simplicial complex (s.c.) when

simplices are added to the complex or removed from it

At each stage of fil-tration a simplices isadded (red). The in-tuitive notion of Bettinumbers as the num-ber of k-dimensionalholes is clear in thisrepresentation.

Page 8: Topological Data Analysis Applied to Idiotypic Network · Theoretical introduction Experiment: Topological Data Analysis of Idiotypic NetworkConclusionsAcknowledgements OUTLINE Theoretical

Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

VISUALIZATION OF PERSISTENCE HOMOLOGY: BETTI

BARCODES

Persistent homology represents an algebraic invariant that detects thebirth and death of each topological features. It is advantageous to

encode the persistent homology in the form of a parameterized versionof Betti numbers.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

CLIQUE

A clique of a graph G is a complete subgraph of G (d(G) = 1),and the clique of largest possible size is referred to as amaximum clique.

A maximal clique is a clique that cannot be extended byincluding one more adjacent vertex, meaning it is not a subsetof a larger clique. Maximum cliques are therefore maximalcliqued (but not necessarily vice versa).

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

CLIQUE WEIGHT RANK PERSISTENT HOMOLOGY

(CWRPH)

A recent development in Toplogical Data Analysis (TDA) providing anew approach to the study of weighted networks that allows to recovercomplete and accurate long-range information from noisy redundant

network, by building on persistent homology.

Petri, Giovanni, et al. ”Topological strata of weighted complex networks.”PloS one 8.6 (2013): e66506.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

CWRPH IN A NUTSHELL - JHOLES

Rucco, Matteo, et al. ”jHoles: A tool for understanding biological complexnetworks via clique weight rank persistent homology.” Electronic Notes inTheoretical Computer Science 306 (2014): 5-18.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

TOPOLOGY DRIVEN MODELLING: THE IS METAPHOR

This work has been inspired by...

The S[B] model mimics the interplay capabilities of the immunesystem to identify, classify and learn new patterns.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

IMMUNE SYSTEM: THE IDIOTYPIC NETWORK

Idiotypic network is formedby a chain of antibodies Abs.Two Abs are connected ifand only if they showAffinity

An increase in the first an-tibody, AB1, recognized byAB2, would lead to an in-crease of the latter. Thesame would be seen regard-ing AB2, AB3, and so forth,always showing a tendencyto restore the equilibrium ofthe system: immune mem-ory

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

EXPERIMENTAL SETUP

Idiotypic Network has been simulated by the agent model basedsimulator C-ImmSim. Two simulations have been executed, inthe first simulation the antigen has been injected only oncewhile in the second simulation the injection has been executedtwice and repeated with three configurations: [Ag2] = [Ag1],[Ag2] > [Ag1], [Ag2] < [Ag1]

Graph pre-processing has been computed with Matlab, whileTDA has been executed by jHoles.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

FROM AFFINITY TO COEXISTENCE

The Idiotypic Network is represented as a weighted graph wherethe weight function is the pairwise Hamming distance betweenantibodies: the Affinity - Aff (Abi,Abj) matrix.

Insted of Aff (Abi,Abj) it is possible to use the so-calledcoexistence function CAbi,j(t):

CAbi,j(t) =Aff (Abi(t),Abj(t)) ∗ [Abi(t)] ∗ [Abj(t)]∑n

k=1[Abk(t)](1)

For lower values of Affinity the concentration must be moresignificant, the match between antibodies is less probable.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

PERSISTENT ENTROPY

Instead of computing an entropy for graph I defined anentropy Shannon-like based on persistent homology.

Def Persistent entropy: given a filtered topological space equipped with anascending filtration algorithm, the set of filtration value F and thecorresponding persistence bar-code B = [aj ; bj] : j ∈ J. A persistent line in abar-code is conventionally represented as [aj ; ∞) here it is substitute with[aj ;m) where m=(max{F}+ 1).

E(F) = −∑j∈J

pjlog(pj) (2)

Where pj = lj/L, lj = bj − aj, and L =∑

j∈J lj

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

REMARKS ON PERSISTENT ENTROPY

From an information-theoretic view point, we have to interpretthe number of significant intervals as the coding length.Entropy measures how different bars of the barcodes are inlength. A barcode with uniform lengths has small entropy.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

AVERAGE PERSISTENT ENTROPY VERSUS TIME [TICK]

Left: IS stimulated once. Right: IS stimulated twice.A peak indicates the immune activation, the plateau indicates theimmune memory.

Statistics over 100 trials.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

TOPOLOGICAL-HOLES ANALYSIS: COMMUNITIES

DETECTIONTopological-holes are formed by generators:0,1,2,. . . ,n-simplices.From the loop frequency analysis we found a loop present inboth the immune responses and in the immune memory: [1, 2] +[2, 7] + [7, 13] + [1, 13].

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

CONCLUDING REMARKS

TDA efficiently recognizes the persistent holes and theirgenerators: the antibodies and how Abs are connected. Itscomputational complexity in the worst case is O(n2)

Persistent entropy allows to study the roles of the persistentantibodies highglighting that they have the central role both inthe functional and connectivity stability of the networks.

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

REFERENCES

I Merelli, Emanuela, and Mario Rasetti. ”The immunesystem as a metaphor for topology driven patternsformation in complex systems.” Artificial ImmuneSystems. Springer Berlin Heidelberg, 2012. 289-291.

I Petri, G., et al. ”Homological scaffolds of brain functionalnetworks.” Journal of The Royal Society Interface 11.101(2014): 20140873.

I Felice, Domenico, Stefano Mancini, and Marco Pettini.”Quantifying networks complexity from informationgeometry viewpoint.” Journal of Mathematical Physics55.4 (2014): 043505.

I Felice, Domenico, et al. ”A geometric entropy measuringnetworks complexity.” arXiv preprint arXiv:1410.5459(2014).

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Theoretical introduction Experiment: Topological Data Analysis of Idiotypic Network Conclusions Acknowledgements

ACKNOWLEDGEMENTS

We acknowledge the financial support of the Future and EmergingTechnologies (FET) programme within the Seventh Framework Programme(FP7) for Research of the European Commission, under the FP7FET-Proactive Call 8 - DyMCS, Grant Agreement TOPDRIM, numberFP7-ICT-318121.


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