of the Max - MDC
of the Max - MDC
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