Prof. Peter Csermelyand the LINK-Group

Semmelweis University, Budapest, Hungary

Crisis responsesand crisis management

What can we learn from biological networks?

www.linkgroup.huinfo@linkgroup.hu

How can we learn from biological networks?

Watts & Strogatz,1998

Networks have general properties• small-worldness• hubs (scale-free degree distribution)• nested hierarchy• stabilization by weak links

Karinthy,1929

Generality of network properties offers• utilization of billion-years crisis experience• judgment of importance• innovation-transfer across different layers of complexity

Barabasi & Albert, 1999

Csermely, 2004; 2009

Crisis-prevention in different systems:example to break conceptual barriers

ecosystem, market, climate• slower recovery from perturbations• increased self-similarity of behaviour• increased variance of fluctuation-patternsNature 461:53

Aging is an early warning signal of a critical transition:

Prevention: elements with less predictable behaviour• omnivores, top-predators• market gurus • stem cells

Farkas et al., Science Signaling 4:pt3

death

Problem solver: specialized to a task, predictablechange of roles

Creative: few links to hubs, unexpected re-routing, flexible, unpredictable

Distributor: hub, specialized to signal distribution, predictable

Csermely, Nature 454:5TiBS 33:569TiBS 35:539

Creative nodes:life-insurance of complex systems

The creative person has an insatiable appetite to discover new and new network environments

The creative person is anetwork-entrepreneur in a Schumpeterian sense

For this the creative person needs a continuous refocusing

in the social categories (dimensions)

By this refocusing the creative person• understands others better• let others know her/his values better• connects isolated people• and exponentially enriches her/himself.Moreover: this is a self-amplifying circle.

Creative amino acids• centre of residue-network• in structural holes

Detoxifying protein

drug-binding detoxification

Creative proteins• stress proteins• signaling switches

Creative cells• stem cells• our brain

Creative persons• firms• societies

A creative person always lets others A creative person always lets others go to the centre – to remain freego to the centre – to remain free

mobile

Csermely, Nature 454:5TiBS 33:569TiBS 35:539

networks:• STRING 7 (5329/190018)

• BioGRID (5329/91749)

• Ekman (2444/6271)

mRNA expressionrestingprotein weight

resting link-weight

multiplication

weights:• equal units• proteins (Nature 441:840)

• mRNA-s (Cell 95:717)

13 stress conditions, 65 experiments(Gasch et al, Mol. Biol. Cell 11:4241)

averagestress

discreteweights

continuousweights

average

uniquestress

6 stress conditions, 32 experiments(Causton et al, Mol. Biol. Cell 12:323)

stressedprotein weight

stressed link-weight

multiplication

average

Network changes in cellular crisisNetwork changes in cellular crisisa short intro to the messy life of cells

analysis of overlapping network modules:ModuLand method

Mihalik & CsermelyPLoS Comput. Biol. 7:e1002187

influencezones of allnodes/links

networkhierachy

communitiesas landscape hills

Kovacs et al, PLoS ONE 5:e12528www.linkgroup.hu/modules.phpnetwork of network scientists; Newman PRE 74:036104

available as a Cytoscape

plug-in

communitycentrality:a measureof the influenceof all other nodes

communitylandscape

shows the centre of

modules too!

The ModuLand method family detectsoverlapping network communities

Community centrality reflectsnode-(link)-importance in crisis-survival

proteinsynthesis

energydistribution

energydistribution

proteindegradation

survivalprocesses

• yeast protein-protein interaction network: 5223 nodes, 44314 links• stress: 15 min 37°C heat shock• link-weight changes: mRNA expression level changes

Mihalik & CsermelyPLoS Comput. Biol. 7:e1002187

communitycentrality

Mihalik & Csermely PLoS Comput. Biol. 7:e1002187

Changes of yeast interactome in crisis:a model of systems level adaptation

• BioGrid yeast interactome: 5223 nodes, 44314 links• stress: 15 min 37°C heat shock + Gasch et al. MBC 11:4241• link-weight changes: mRNA expression level changes

Stressed yeast cell:• nodes belong to less modules• modules have less intensive contactssmaller overlaps between modules,more condensed modules

Consequences of network crisisConsequences of network crisis

Szalay et al, FEBS Lett. 581:3675; Palotai et al. IUBMB Life 60:10Mihalik and Csermely PLoS Comput. Biol. 7:e1002187

stress increased network flexibility• spared links• noise and damage localization• modular independence: larger response-space and better conflict management

celldeath

networkdesintegrationcreative

elements*

Crisis survival: creative elements

*Schumpeterian creative destruction

Bacteria living in a variable environment have more separate network modules

Parter, Kashtan & AlonBMC Evol. Biol. 7:169

larger environmental variability

moreseparatemodules

metabolic networksof 117 bacteria

Bacteria living in a variable environment have more separate network modules

Szalay-Bekő et al.arxiv.org/1111.3033

Multimodular metabolic network

of the free living E. coli

communitylandscapes(red/yellow: tops)

Single major core of the metabolic networkof the symbiont Buchnera

Telecommunication network modules become more cohesive in social crisis

more than 10 million peopleBagrow, Wang & BarabasiPLoS ONE 6:e17680

time

phonecall

intensity

cohesive modules

diffuse modules

in crisis we call our motherand not a distant friend…Vassy, Wang, Barabasi & Csermely

in preparation

Physica A 334:583Csermely: Weak Linksstress

assembly >disassembly

disassembly >assembly

network diameterdegrees of

freedom

Topological phase transitions reflect the overlap-decrease at one level higher

Generality: emergence of two phenotypesGenerality: emergence of two phenotypes• ecosystems: food limitation see otters, patchiness in drought

• brain: modular reorganization in learning

• social networks: broker stress, Schumpeterian creative destruction Haldane & May: US Volcker Rule separates bank system modules

Many resources: large phenotypeMany resources: large phenotypefew resources: small phenotypefew resources: small phenotype

Bateson et al.Nature 430:419

Metabolism: large: rapid, overspendingsmall: slow, ‘thrifty’‘overeating’ society: diabetes

Janos Kornai: Thoughts about capitalism (in Hungarian, in preparation in English)

Society: large: capitalismsmall: socialismsurplus and shortage economies

Draghi, Parsons,Wagner & Plotkin, Nature 463:353

all phenotypescan be reached

5% of phenotypescan be reached

effect of adaptation++

possibility of adaptation++

‘small’ ‘balanced’ ‘large’

Low adaptation potential Low adaptation potential of ‘small’ and large’ of ‘small’ and large’ phenotypesphenotypes

stress, crisis

Take-home messages

1.

2. Community rearrangements may be a generalmechanism of system level adaptation

Biological networks offer the experience ofbillion years in crisis-survival

effect of adaptation++

possibility of adaptation++

‘small’ ‘balanced’ ‘large’

stress, crisis

A network componentof evolvability?

István A. Kovács

Máté Szalay-Bekő

ÁgostonMihalik

Stress

ModuLand

RobinPalotai

potential newcollaborators

Acknowledgments

Gábor I. Simkó

Games

Shijun Wang

www.linkgroup.huinfo@linkgroup.hu

AndrásLondon

MarcellStippinger

Aging

Peter Csermely:Weak Links

Springer, 2009

available free:

Google-books

Zsolt Vassy

starting node

community-44: 1127 schoolchildren, 5096 friendships; Add-Health

influence zones

Influence zonesusing the NodeLand method