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of the Max - MDC

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Visualization <strong>of</strong> <strong>the</strong> UniHi interaction network. Dots represent proteins, lines <strong>the</strong>ir interactions. The source database <strong>of</strong> interactions<br />

is indicated by different colours. Dark blue – <strong>MDC</strong>-Y2H; Red – Reactome; Dark green – Ophid; Light green – HomoMINT. Grey – overlapping<br />

proteins and interactions from more than one data source.<br />

<strong>the</strong>se studies, we could identify novel pathway modulators<br />

and provide a first protein interaction network for <strong>the</strong> MAPK<br />

and Akt signalling pathways.<br />

In collaboration with Pr<strong>of</strong>. Marc Vidal from Harvard Medical<br />

School, Boston, we have established a new conceptional<br />

framework for “self-controlled” interactome mapping. Gold<br />

standard positive (GSP) and negative (GSN) training sets <strong>of</strong><br />

binary protein-protein interactions were established for validation<br />

<strong>of</strong> our interaction screening technology and repeated<br />

Y2H interaction screens were performed under highly<br />

controlled conditions. Criteria for future systematic interaction<br />

mapping projects such as completeness, detectability,<br />

coverage and specificity were defined and <strong>the</strong> size <strong>of</strong> <strong>the</strong><br />

human binary interactome network was calculated. We estimate<br />

that, assuming <strong>the</strong>re are about 22,000 protein-coding<br />

genes in <strong>the</strong> genome and excluding protein is<strong>of</strong>orms, which<br />

add complexity, <strong>the</strong> human interactome contains about 2.5<br />

million binary interactions, <strong>the</strong> vast majority <strong>of</strong> which<br />

remain to be mapped. We could also demonstrate that Y2H<br />

datasets produced with full-length proteins are superior in<br />

specificity to literature curated datasets, suggesting that<br />

high-throughput Y2H screening is <strong>the</strong> optimal method for<br />

mapping a significant portion <strong>of</strong> <strong>the</strong> human interactome.<br />

This work will be <strong>the</strong> conceptional basis for an international<br />

interactome mapping project.<br />

Function and Dysfunction <strong>of</strong> <strong>the</strong> Nervous System 165

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