Algorithmic systems biology propels nutrigenomics Marco Scotti September 16th, 2010 Centre for Computational and Systems Biology The Microsoft Research

Algorithmic systems biology propels nutrigenomics Marco Scotti

September 16th, 2010

Centre for Computational and Systems BiologyThe Microsoft Research - University of Trento

Scotti - Roma, September 16th, 2010


• Nutrigenomics and personalized diet

• Algorithmic systems biology in nutrigenomics

• Sustainable health: nutrigenomics and environment

• Ecological networks to predict risks of secondary extinctions

• Simulations and network analysis for dealing with a multi-scale approach

Overview


What is nutrigenomics?


DNA methylation, cancer and nutrients

• DNA methylation is an effective suppressor of gene expression

• Changes in methylation patterns may contribute to the development of cancer

• Dietary factors that are involved in folate cycle provide the most compelling data for the interaction of nutrients and DNA methylation

• Micronutrients that influence the supply of methyl groups are folate (vitamin B9), vitamin B12, vitamin B6, methionine, chlorine, selenium and alcohol


Davis, CD & Uthus, EO. Exp. Biol. Med. 229, 988-995 (2004)

Folate cycle and cancer


Folate and cancer prevention

Folate (vitamin B9) is thought to play a significant role in cancer prevention

Folate deficiency:

• Decreases intracellular S-adenosylmethionine (SAM) which inhibits cytosine methylation in DNA

• Activates proto-oncogenes

• Induces malignant transformations

• Causes DNA precursor imbalances

• Misincorporates uracil into DNA

• Promotes chromosome breakage


Folate and ethanol

Mason, JB & Choi, SW. Alcohol 35, 235-241 (2005)


Folate and cancer risk: timing and dose

Although increases in folate before the existence of preneoplastic lesions (such as aberrant crypt foci or polyps in the colon) can prevent tumor development, supplementation with synthetic folic acid may enhance progression once preneoplastic lesions are present

Ulrich, CM. Am. J. Clin. Nutr. 86, 271-273 (2007)


Folate and MTHFR C677T polymorphism

Ueland, PM et al. Trends in Pharmacological Sciences 22, 195-201 (2001)

MTHFR polymorphism affects the distribution between folate species (green) used for DNA and RNA syntheses, or protein synthesis


CROP (apple) HUMAN (health)POLLINATOR (fitness)

Nutrition and sustainability


Healthy and sustainable diets

Human health

Environmental sustainability

A B

C D

A – B – C – D

D – B – C – A

Scotti - Roma, September 16th, 2010James, DG & Grasswitz, TR. BioControl 50, 871-880 (2005)

HIPV

VP

Generalist predator

Specialist parasitoid

Herbivore

Food in agro-ecosystems


Ecological networks

Food webs are schematic representations of who eats whom in ecosystems

Host-parasitePlant-ant

Plant-seed disperserPlant-pollinator


Rooted food webs

• The energy that sustains ecosystems comes from outside the system (i.e., solar radiation)

• We can connect every primary producer with this "Root" node

• Mapping the extent of secondary extinctions is equivalent to measuring how many nodes will be disconnected from the “Root” node, when an extinction occurs


Secondary extinctions

As human activity threats the functioning of ecological systems (by habitat destruction, fragmentation, possibly causing climate change and invasions) we face the problem of how to understand and hopefully manage primary and secondary extinctions


Dominator tree

Food web

Dominator tree

Dominator tree unfolds the complex food web architecture, yielding a simpler topology made of linear pathways that are essential for energy delivery


The Ythan Estuary is the tidal component of the Ythan River, emptying into the North Sea approximately 19 kilometres north of Aberdeen, Scotland

Ythan Estuary

Food web Dominator tree

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Ythan96

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Error Sensitivity (ES) = the fraction of species that would go extinct following a random removal

Attack sensitivity (AS) = it represents the maximum damage that we can make with a single node removal. AS ranges between 0 and 1

Error and attack sensitivity


Where are the clusters and who is in them?

Who is in the core of the network?

Who are the connectors, generalists and specialists?

Who is on the periphery?

Node centralities

Closeness Centrality

Degree Centrality

Betweenness Centrality


Fragility in ecosystems

Grass

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Agro-ecosystem

Natural-ecosystem

Mangroves

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Degree distribution

SubgraphCentrality

Diameter 2

Density 0.4

Local and global properties

Algorithmic systems biology propels nutrigenomics Marco Scotti

[email protected]

September 16th, 2010

Centre for Computational and Systems BiologyThe Microsoft Research - University of Trento


Documents

Algorithmic systems biology propels nutrigenomics Marco Scotti September 16th, 2010 Centre for Computational and Systems Biology The Microsoft Research