Genomatix integrates genome-wide open chromatin from next generation sequencing

Feb 26 2008

Genomatix Software GmbH, a Systems Biology company focussed on high quality annotation and the understanding of gene regulation, has begun showcasing its abilities in the analysis of data generated by Next Generation Sequencing (NGS) technology.

Allan P. Boyle et al published in the January 2008 issue of Cell some remarkable work on “High-Resolution Mapping and Characterization of Open Chromatin across the Genome” where they identified DNase I hypersensitive sites from primary human CD4+ Cells. Those samples were sequenced using both the Illumina Solexa and Roche 454 NGS platforms.

Genomatix applied its NGS analysis pipeline to the Illumina Solexa data as deposited at the Gene Expression Omnibus and made the results publicly available.

Out of the roughly 15 million 20mer sequence tags, the Genomatix proprietary ultra fast mapping capability delivered over 11 million (75%) unique positions in less than two hours, allowing up to three point mutations and two insertions/deletions.

Effective noise filtering was performed by sequence tag clustering at different levels of stringency. Genome wide correlation studies show that the majority of open chromatin is located in intergenic and intronic regions.

Additionally a strong correlation is shown between open chromatin and the Genomatix promoter annotation. Distance correlations of sequence tags and transcriptional start sites give further experimental confirmation to the longstanding Genomatix definition of a proximal promoter, spanning from -500 base pairs from TSS to + 100 base pairs downstream of TSS. The analyses show the frequent use of alternative promoters for alternative transcripts within the same gene locus, as postulated by Genomatix since its first genome wide promoter annotations in 2000.

Genomic localization of identified sequences in context with other genomic annotations like transcripts, promoters, TSS, microRNAs, etc. can be accessed by all Genomatix customers and subscribers to a no charge evaluation account to the ElDorado extended genome annotation database.

Dr. Martin Seifert, Vice President Business Development and Consulting at Genomatix says: “We are excited about the power and wealth of all the new data being delivered by NGS technology. We have everything in place to analyze all these data and integrate them into our ElDorado annotation database today…something we can do within hours of starting an analysis. The real value is realized by overlaying and correlating all this data that has been derived by different approaches, for example, the open chromatin data correlated with chromatinIP tags for several nuclear receptors, expression profiles, microRNAs and all the wealth of other information in our databases that give an excellent handle on localizing and elucidating the role of enhancers/repressors in intergenic regions.”

Dr. Seifert continues: ”Several in-house projects which we conducted for customers demonstrate the clear superiority of our rich data content, our proprietary approaches, and open and modular architecture. With the emergence of NGS, the outstanding value of our technology is now more evident than ever!”