the following two papers Taguchi, Y.-h.; Dharshini, S.A.P.; Gromiha, M.M. Identification of Transcription Factors, Biological Pathways, and Diseases as Mediated by N6-methyladenosine Using Tensor Decomposition-Based Unsupervised Feature Extraction. Appl. Sci. 2021, 11, 213. https://doi.org/10.3390/app11010213 Roy, S.S., Taguchi, YH. Identification of genes associated with altered gene expression and m6A profiles during hypoxia using tensor decomposition based unsupervised feature extraction. Sci Rep 11, 8909 (2021). https://doi.org/10.1038/s41598-021-87779-7
in eukaryotes. It is also known to be related to various biological functions including • Alternative splicing • Transfer from nuclei to cytoplasm • Translation • Stability • Transcription That is, m6A affects almost all aspects of RNA.
the function of m6A well. We discuss the following two topics of m6A in this talk. 1. How does m6A affect other biological factors, e.g., transcription factors, biological pathways, and diseases ? 2. Specifically, how does m6A affect hypoxia ? Method: Tensor decomposition
Vector x i : a set of scholars in line Matrix x ij : a set of scholars aligned in a table (i.e. rows and columns) Tensor x ijk : a set of scholars aligned in an array more then two rows x ijk i j k 1 (1,2,3,4,...) (1 2 3 4 5 6 7 8 9 )
series of product of vectors, x ijk i:genes j:persons k:tissues G k j i l 1 l 2 l 3 = u l 1 i u l 2 j u l 3 k u l 1 i u l 2 j u l 3 k x ijk ≃∑ l 1 =1 L 1 ∑ l 2 =2 L 2 ∑ l 3 =1 L 3 G (l 1 l 2 l 3 )u l 1 i u l 2 j u l 3 k
of x ijk upon i” → u l1i “Dependence of x ijk upon j” → u l2j “Dependence of x ijk upon k” → u l3k ← Healthy control vs patient ← tissue specificity Gene selection ↑ We can answer the question : Which genes are expressed between healthy controls and patients in tissue specific manner?
and gene expression, were measured with and without METTL3 KO. They are attributed to genes as well. Purpose: Purpose: Which genes are associated with histone modifications, m6A and gene expression, altered by METTL3 KO?
four commonly selected diseases Disease Perturbations from GEO down Disease Perturbations from GEO down "Crohn’s disease DOID-8778 human GSE6731 sample 757"; "Ulcerative Colitis C0009324 human GSE6731 sample 249"; "Ulcerative colitis DOID-8577 human GSE6731 sample 759"; "Ulcerative colitis DOID-8577 human GSE6731 sample 760"; "Hepatitis C DOID-1883 human GSE20948 sample 599"; "Diabetic Nephropathy C0011881 human GSE1009 sample 223"; "Cardiac Hypertrophy C1383860 rat GSE1055 sample 354"; "Prostate cancer DOID-10283 human GSE3868 sample 639"; "Hepatitis C DOID-1883 human GSE20948 sample 597"; "Cancer of prostate C0376358 human GSE3868 sample 135" Disease Perturbations from GEO up Disease Perturbations from GEO up "Pancreatitis DOID-4989 mouse GSE3644 sample 513 Asthma"; "Allergic C0155877 human GSE3004 sample 360"; "Acute pancreatitis C0001339 mouse GSE3644 sample 376"; "Chronic lymphocytic leukemia DOID-1040 human GSE6691 sample 786"
Using TD, we could identify common genes associated with histon modification, m6A, gene expression altered with METTL3 KO, and common TFs that regulated these genes and common diseases associated with altered expression of these genes between human and mouse.
was applied to gene expression gene expression Singular value vectors attributed to time points when TD was applied to m6A profiles m6A profiles 2nd ones are correlated with times and are common between gene expression and m6A profiles
genes (based on gene expression) and 200 genes (based on m6A) selected by applying KTD-based unsupervised FE to integration of gene expression and m6A profile. Fifteen terms with adjusted P-values less than 0.05 are listed. Hypoxia-inducible factor 1 Hypoxia-inducible factor 1
We have successfully integrated gene expression and m6A profiles at four time points in response to hypoxia. Genes associated with time development are related to HIF-1 signaling pathway. m6A likely regulated hipoxia through gene expression regulated by m6A.