BioSapiens Deliverable 11.2

Functional modules for human chromosome 21

Introduction

The latest version of the STRING database, version 6.2, integrates four curated databases of pathways and complexes, five protein interaction databases, microarray expression data from SMD, literature mining of Medline ab stracts, and results three genomic context methods. Probabilistic quality scores are provided for each individual interaction and evidence source. In the present pilot study, we have identified functional modules possibly related to Down's Syndrome by app lying clustering methods the STRING network for human proteins encoded by chromosome 21.

Methods

A list of 395 proteins encoded by human chromosome 21 was extracted from Ensembl. These correspond to 192 locus representative proteins in the STRING database. A similarity matrix was constructed by calculating the probability of the most probably path in the STRING network that connects any two of the 192 proteins. The proteins were clustered according to this similarity matrix using the single linkage clustering algorithm. A functional association network for each cluster was extracted from the STRING d atabase. These were subsequently expanded by including the closest neighbours according to the most probably paths matrix; at this step proteins not located on chromosome 21 were also included.

Example modules

Below, eight of the clusters are shown. Two levels of network expansion is provided for each cluster as well as a list of Ensembl proteins belonging to the cluster.

Steroid and terpenoid biosynthesis

[Expanded 1] [Expanded 2] [List]

Collagenases, metalloproteinases and inhibitors

[Expanded 1] [Expanded 2] [List]

Voltage-gated potassium channels

[Expanded 1] [Expanded 2] [List]

Prostaglandin metabolism

[Expanded 1] [Expanded 2] [List]

Cathepsins and Cystatins

[Expanded 1] [Expanded 2] [List]

Chromatin assembly and anti-silencing

[Expanded 1] [List]

Phosphatidylinositol N-acetylglucosaminyltransferase complex

This cluster contains Down syndrome critical region protein 5 (DSCR5) and reveals a link to Down syndrome critical region protein 6 (DSCR6) upon expansion.

[Expanded 1] [Expanded 2] [List]

Biotin metabolism and lysine degradation

[Expanded 1] [Expanded 2] [List]

Last updated by Lars Juhl Jensen on 31 June 2005.