Unsupervised tensor decomposition-based method to extract candidate transcriptionfactors as histone modification bookmarks in post-mitotic transcriptional reactivation

Presentation at InCob2020
https://incob.apbionet.org/incob20/
25th Nov. 2020
Presentation video
https://youtu.be/1r4ZXbSiI_Q

Transcript

1. Unsupervised tensor decomposition-based method to extract candidate transcriptionfactors as histone modification bookmarks in post-mitotic transcriptional reactivation Y-h. Taguchi Department of Physics, Chuo University, Tokyo, Japan Turki Turki Department of Computer Science, King Abdulaziz University, Jeddah, Saudi Arabia bioRxiv https://www.biorxiv.org/content/10.1101/2020.09.23.309633v1
2. Introduction Transcription ← ⨉ → DNA replication ⇓ DNA replication ⇒ “Transcription → ⨉” ⇓ Genome state (TF binding, histone modification) → Reset? ⇓ No, should be bookmarked bookmarked ! ⇓ But how?
3. whole-genome histone modification profile GSE141081 x ijkms ∈ℝN ×2×4×3×2 ⇒ formatted as tensor i: genome regions of 25,000 bps j: cell lines 1:RPE1, 2:USO2 k: histone modification 1: H3K27ac, 2: H3K4me1, 3: H3K4me3, 4: input m:cell cycle 1:interphase, 2:prometaphase, 3 :anaphase/telophase s:replicates
4. Tensor decomposition (Tucker) by higher order singular value decomposition (HOSVD) x ijkms x ijkms ≃∑ l 1 =1 2 ∑ l 2 =1 4 ∑ l 3 =1 3 ∑ l 4 =1 2 ∑ l 5 =1 N G(l 1 l 2 l 3 l 4 l 5 )u l 1 j u l 2 k u l 3 m u l 4 s u l 5 i G u l 2 k u l 3 m ≃ • • • • • • u l 1 j
5. ∑ l 1 =1 2 ∑ l 2 =1 4 ∑ l 3 =1 3 ∑ l 4 =1 2 ∑ l 5 =1 N G(l 1 l 2 l 3 l 4 l 5 )u l 1 j u l 2 k u l 3 m u l 4 s u l 5 i l 1 =1: no dependence upon cell lines 2 ≤ l 2 ≤4: some dependence upon histone modification l 3 =3: most significant reactivation during phases l 4 =1: no dependence upon replicates ∑ l 2 =2 4 G(1,l 2 ,3,1,l 5 )2 l l 5 5 =4 =4
6. Dependence upon cell cycle Reactivation Reactivation l l 3 3 =1 =1 l l 3 3 =2 =2 l l 3 3 =3 =3
7. control Histone modification dependence l l 2 2 =1 =1 l l 2 2 =2 =2 l l 2 2 =3 =3 l l 2 2 =4 =4
8. Cell line dependence Replicate dependence l l 1 1 =1 =1 l l 4 4 =1 =1
9. ∑ l 2 =2 4 G(1,l 2 ,3,1,l 5 )2 l l 5 5 =4 =4
10. Attributing P-values to ith genomic region P i =P χ2 [> (u 4 i σ4 )2] Cumulative chi squared distribution Assuming that u 4i obeys Gaussian
11. 507 DNA regions : BH criterion corrected P values less than 0.01 ⇓ 525 gene symbols are included
12. Are these genes associated with histone modification coincident with re-activation or bookmark?
13. Enrichment analysis TFs binding
14. Some biologically critical TFs are included.
15. Some biologically critical TFs are included.
16. Top 10 most frequently listed transcription factor (TF) families These are candidate bookmark TFs! These are candidate bookmark TFs!
17. Conclusion • Bookmark mechanism of reactivation of transcription after DNA duplication was studied. • TD based unsupervised FE was applied to three histone modification profiles before/after DNA replication • Some candidate bookmark TFs were identified.