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Assessing Computational Methods for
Transcription Factor Target Gene Identification
Based on ChIP-seq Data
Advisor: Dr. Chun-Chi Liu
Speaker: Yu-Jung Chiu
Date: 2015/6/15
1
Outline
• Introduction
• Materials and Methods
• Results
• Discussion
2015/6/18 2
Introduction
2015/6/18 3
ChIP-Seq
4Mardis E, Nature Methods (2007)
Peter J. Park, Nature Reviews (2009)
2015/6/18
Peak
2015/6/18 5
Reference genome
3 2
Peter V Kharchenko, Nature(2008)
Binding Profile
2015/6/18 6
Chao Cheng, NAR(2011)
2015/6/18 7
Materials and Methods
ChIP-seq data
• HemoChIP (hematopoietic cells):
30 transcription factors
• ESChIP (embryonic stem cells):
15 transcription factors
2015/6/18 8
Expression data
• HemoChIP : 30 expression data
• ESChIP : 15 expression data
2015/6/18 9
scoring procedure
2015/6/18 10
TF-target prediction methods
2015/6/18 11
2015/6/18 12
Results
Perturbation expression data
2015/6/18 13
Differential TF activity data
2015/6/18 14
Functional homogeneity of targets
2015/6/18 15
Consistency and specificity of target predictions
2015/6/18 16
Gene density around predicted targets
2015/6/18 17
2015/6/18 18
Discussion
Discussion
• Out of six compared methods, Binary and Chen clearly
performed the worst.
• other methods performed similarly, but we observed a
small advantage of ClosestGene especially in the
expression data tests and GO enrichment.
• all of our analysis is based on mouse data , similar
assessments should be performed for other species.
2015/6/18 19
2015/6/18 20
Thank You
Supplementary
2015/6/18 21

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615seminar

Editor's Notes

  1. Overlap of the top 500 targets with the top 500 genes differentially expressed in (A) HemoChIP and (B) ESChIP TF perturbation experiments.
  2. Overlap of the top 500 targets with the top 500 genes differentially expressed (C) between erythroid and myeloid cells or (D) between undifferentiated (ES) and differentiated (MEF) cells. we expected (based on the function of the TF) that a given TF would change its activity.
  3. Number of significantly enriched GO terms specific for a given cellular system and specific for the opposite cellular system for HemoChIP (A) and ESChIP (B). The specific terms are hematopoiesis or embryonic development related GO terms for HemoChIP and ESChIP, respectively.
  4. Gene dense regions tend to contain more binding events (peaks) than gene sparse regions of the genome. The figure shows gene density (number of genes inside 1 Mb regions around the target gene’s TSS) of the regions harboring the top 500 genes across the studies in the (A) HemoChIP and (B) ESChIP datasets.