gene regulatory network inference. progress in disease treatment personalized medicine is becoming...
TRANSCRIPT
![Page 1: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/1.jpg)
Gene Regulatory Network Inference
![Page 2: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/2.jpg)
Progress in Disease Treatment
Personalized medicine is becoming more prevalent for several kinds of cancer treatment
10-Feb-2009 – Breast Bioclassifier developed at the Huntsman Cancer Institute 1/8 women will be diagnosed with breast cancer Microarray analysis can separate large group who
need no treatment Savings in cost and lifestyle With $100 human genomes, doctors can determine
which drugs will be effective for your genotype
![Page 3: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/3.jpg)
Biological Networks
Gene regulatory network: two genes are connected if the expression of one gene modulates expression of another one by either activation or inhibition
Protein interaction network: proteins that are connected in physical interactions or metabolic and signaling pathways of the cell;
Metabolic network: metabolic products and substrates that participate in one reaction;
![Page 4: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/4.jpg)
Background Knowledge
Cell reproduction, metabolism, and responses to the environment are all controlled by proteins;
Each gene is responsible for constructing a single protein;
Some genes manufacture proteins which control the rate at which other genes manufacture proteins (either promoting or suppressing);
Hence some genes regulate other genes (via the proteins they create) ;
![Page 5: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/5.jpg)
What is Gene Regulatory Network?
Gene regulatory networks (GRNs) are the on-off switches of a cell operating at the gene level.
Two genes are connected if the expression of one gene modulates expression of another one by either activation or inhibition
An example.
![Page 6: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/6.jpg)
Sources: http://www.ornl.gov/sci/techresources/Human_Genome/graphics/slides/images/REGNET.jpg
![Page 7: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/7.jpg)
Why Study GRN?
Genes are not independent; They regulate each other and act collectively; This collective behavior can be observed using
microarray; Some genes control the response of the cell to
changes in the environment by regulating other genes;
Potential discovery of triggering mechanism and treatments for disease;
![Page 8: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/8.jpg)
Learning Causal Relationships
High-throughput genetic technologies empowers to study how genes interact with each other;
If gene A consistently turns on after Gene C, then gene C may be causing gene A to turn on
We have to have a lot of carefully controlled time series data to infer this
![Page 9: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/9.jpg)
Kegg
http://www.genome.jp/kegg/pathway.html
![Page 10: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/10.jpg)
Pathgen
![Page 11: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/11.jpg)
Microarray data
Gene up-regulate, down-regulate;
Genes
Samples
![Page 12: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/12.jpg)
Learning from microarray data
Recurrent Neural Networks Bayesian learning approaches
![Page 13: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/13.jpg)
AIRnet: Asynchronous Inference of
Regulatory networks
1. Classify gene levels using k-means clustering
2. Compute influence vectors (i.v.)
3. Convert i.v.'s into a sorted list of edges
4. Use Kruskal's algorithm to find the minimum-cost spanning
tree
![Page 14: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/14.jpg)
Influence Vectors
1. Perform pairwise-
comparisons of change in
gene levels between
samples, adding or
subtracting from i.v.
2. Divide i.v. by the total
number of comparisons
![Page 15: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/15.jpg)
Clockwise from top left: simulated E.coli 1 network;E.coli 1 inferred correlations above 50%;simulated E.coli 2 network;E.coli 2 inferred correlations above 50%;
inferred networks made using 2 bins for each gene.
![Page 16: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/16.jpg)
Euploid network →
← Trisomic network
![Page 17: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/17.jpg)
Graph showing differences between Euploid and Trisomic
![Page 18: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/18.jpg)
Graph highlighting differences between Euploid and Trisomic
using multiple datasets
![Page 19: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/19.jpg)
DREAM in-silico challenge
![Page 20: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/20.jpg)
Using phylogenetic profiles to predict protein function
Basic Idea: Sequence alignment is a good way to infer protein function, when two proteins do the exact same thing in two different organisms.
But can we decide if two proteins function in the same pathway?
Assume that if the two proteins function together they must evolve in a correlated fashion: every organism that has a homolog of one of the
proteins must also have a homolog of the other protein
![Page 21: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/21.jpg)
Phylogenetic Profile
The phylogenetic profile of a protein is a string consisting of 0s and 1s, which represent the absence or presence of the protein in the corresponding sequenced genome;
Protein P1: 0 0 1 0 1 1 0 0Protein P2: 0 0 1 0 1 1 0 0Protein P3: 1 0 0 1 0 1 0 0
For a given protein, BLAST against N sequenced genomes.
If protein has a homolog in the organism n, set coordinate n to 1. Otherwise set it to 0.
![Page 22: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/22.jpg)
Phylogenetic Profile
Proteins
Species
![Page 23: Gene Regulatory Network Inference. Progress in Disease Treatment Personalized medicine is becoming more prevalent for several kinds of cancer treatment](https://reader033.vdocuments.us/reader033/viewer/2022051621/56649e895503460f94b8db03/html5/thumbnails/23.jpg)
Pellegrini M, Marcotte EM, Thompson MJ, Eisenberg D, Yeates TO, Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc Natl Acad Sci U S A. 96(8):4285-8,. 1999