Genomatix Regulatory Sequence Analysis
- Registration Closed
- Apr 17, 2018
- 09:30 AM to 05:00 PM
- NIH Library Training Room
Session DescriptionAll day training split between morning and afternoon sessions.
Morning: 09:30 AM - 12 PM
Scientific presentation detailing the principles and introducing the strategy:
MORE mechanistic links from genotype to phenotype: A cornerstone of the regulatory code?
Phenotypes of mammalian organisms are realized and controlled by regulatory networks. Genetic and epigenetic networks influence transcriptional networks that in turn are linked to metabolic and structural networks. Health and disease are based on the same pathways and networks but the gene regulatory networks in fact act quantitatively differently. Transcriptional regulatory networks are at the core of regulatory networks. They integrate external with internal signals and generate the transcriptional response of cells and tissues. A great deal of transcriptional control is carried out by the interactions of specific transcription factors whose binding sites are organized into sets within regulatory regions of DNA, such as promoters and enhancers. The spatial structure of such sets of binding sites - more than the binding sites themselves - is the major determinant of when, where, and to what extent a particular transcript of a gene is going to be expressed. These functional sets of binding sites are called Multiple Organized Regulatory Element cassettes (MORE-cassettes), and they encode FUNCTIONAL properties of transcription control as opposed to PHYSICAL properties that reside within the individual TFBSs. MORE-cassettes, the general rules they follow, and how to read their regulatory code from regulatory sequence information will be discussed using a recently published study as background (Rozman et al, Nature Comm., 2018). This large-scale study has shown that phenotype-associated MORE-cassettes allow general phenotypic predictions based solely on their presence in the promoter sequences of candidate genes. This direct link from the macroscopic level of whole organism phenotype to the molecular regulatory code laid down in MORE-cassettes is a unique feature of MORE-cassettes, and paves the way for entirely new applications of omics technologies, e.g. in personalized medicine approaches.
Afternoon: 1:30 PM - 5 PM
Hands on example from the data set published in the Nature Communications paper:
Promoter retrieval using Gene2Promoter
Determination of MORE-cassettes using FrameWorker
Determination of data-association of MORE-cassettes using ModelInspector & other tools
Outline and rational of setting up MORE-sets (demo)