GRIND Gene Regulation INference using Dual thresholding. Ir. W.P.A. Ligtenberg Eindhoven University of Technology

Transcription

1 GRIND Gene Regulation INference using Dual thresholding Ir. W.P.A. Ligtenberg Eindhoven University of Technology

2 Overview Project aim Introduction to network inference Benchmark (ValGRINT) Results GRIND Results Future

3 Project aim Develop an algorithm to infer gene regulation networks from microarray data How to compare different algorithms Is there a benchmark available? No... Develop benchmark Develop algorithm later (fair comparison)

4 Introduction to network inference algorithm Image from:

5 Network inference The importance of keeping track Inputs Outputs - Heat shock - Oxygen deprivation targets multiple inputs AND OR What caused this output to change?

6 Network inference The importance of keeping track Inputs Outputs Knock down gene A targets one input directly AND OR This change is caused by gene A. Directly or indirectly?

7 ValGRINT x5 16 Network Directed Scale Free Network Generator SynTReN KO all genes Repeat 5x Data 16 x Network 1024 Data 1024

8 Benchmark ValGRINT computational data of multiple sizes evaluation of Gene Regulation INference Tools. Computational data Underlying network of biological data is not completely known. If my prediction false? Or have I discovered something new? Flexible Cheap to do more repetitions Multiple sizes Calculation time versus data size Performance versus data size

9 Benchmark ValGRINT Multiple repetitions, interaction types Multiple repetitions Each experiment is repeated 5 times. The whole process for each size or interaction type is repeated 5 times as well Statistics Different interaction types Linear, linearlike, mixed, random, sigmoidal, steep, step Does an algorithm have a certain preference?

10 Existing algorithms Aracne Mutual Information (sort correlation) Data Processing Inequality (to remove indirect edges) Banjo NIR Bayesian networks Fits Linear ODEs to the data Uses an intervention file (what has been knocked down in which experiment)

11 ValGRINT results computation time

12 Comparing results - F-score Count the number of TP, FP, TN, FN F score= 2 precision recall precision recall precision= recall= TP TP FP TP TP FN

13 ValGRINT results Performance vs size

14 ValGRINT results Performance vs interaction

15 GRIND Gene Regulation INference by Dual thresholding Test null hypothesis that mrna levels have not changed after the intervention. Calculate the correlation coefficient between all gene pairs. (across all experiments) Use two different thresholds on the aforementioned values. P-value < 0.01 R > 0.2 Both thresholds should be met Result: Directed (signed) network

16 GRIND genes experiments P-value WT ko1 ko2 ko3 ko4 ko Correlation WT ko1 ko2 ko3 ko4 ko5

17 GRIND results computation time

18 GRIND results Performance vs size

19 GRIND results Performance vs interaction

20 GRIND on a videocard? Correlation matrix calculation has been ported to the GPU (Graphical Processing Unit / videocard) Performance improvement of ~150X Normal Python code took ~500 seconds PyCuda code took ~3 seconds

21 Conclusions Knowledge about the interventions improves results in network inference ValGRINT gives insight into the pro's and con's of the various algorithms We have been succesfull in developing a new algorithm for gene regulation inference (GRIND)

22 Future prospects Extend the GRIND algorithm to also predict importance of genes that have not been perturbed. Implement GRIND on the GPU Investigate other statistical features Use more advanced pattern recognition (this is a very small tree classifier)

23 Project information We have developed software and a benchmark ValGRINT GRIND Not yet submitted to Gforge.nbic.nl We have ongoing collaborations with AMC Mathmetics department Education BioInformatics & OGO Followed the Pattern Recognition course (which was good!) Valorisation No licenses or patents. What am I planning to do next? Projectwise: Extend algorithm, GPU Jobwise: Bioinformatics education, or pattern recognition for a company