ABSTRACT
Topologically associating domains (TADs) are critical structural units in three-dimensional genome organization of mammalian genome. Dynamic reorganizations of TADs between health and disease states are associated with transcription and other essential genome functions. However, computational methods that can identify reorganized TADs are still in the early stages of development. Here, we present DiffDomain, an algorithm leveraging high-dimensional random matrix theory to identify structurally reorganized TADs using chromatin contact maps. Method comparison using multiple real Hi-C datasets reveals that DiffDomain outperforms alternative methods for FPRs, TPRs, and identifying a new subtype of reorganized TADs. The robustness of DiffDomain and its biological applications are demonstrated by applying on Hi-C data from different cell types and disease states. Identified reorganized TADs are associated with structural variations and changes in CTCF binding sites and other epigenomic changes. By applying to a single-cell Hi-C data from mouse neuronal development, DiffDomain can identify reorganized TADs between cell types with reasonable reproducibility using pseudo-bulk Hi-C data from as few as 100 cells per condition. Moreover, DiffDomain reveals that TADs have clear differential cell-to-population variability and heterogeneous cell-to-cell variability. Therefore, DiffDomain is a statistically sound method for better comparative analysis of TADs using both Hi-C and single-cell Hi-C data.
ABSTRACT
Objective To examine the expression of autoantibodies against angiotensin Ⅱ type 1 receptor (AT1-AAs),monocyte chemoattractant protein-1 (MCP-1) and high-sensitivity C-reactive protein (hs-CRP) in patients of acute coronary syndrome (ACS),and study the role of AT1-AAs in plaque stability and pathogenesis of ACS.Methods Sixty patients with ACS were selected as ACS group,60 patients with stable angina pectoris (SAP) were selected as SAP group,and 60 healthy people were selected as control groups.The epitopes of the second extracellular loop of angiotensin Ⅱ type 1 receptor (165-191) were synthesized and used as antigen to screen the serum autoantibodies by enzyme-linked immunosorbent assay (ELISA).The peripheral blood levels of MCP-1 and hs-CRP were also evaluated.Results The positive rates of AT1-AAs in ACS group,SAP group and control group were 45.0％(27/60),21.7％(13/60) and 5.0％(3/60),respectively.The positive rates of AT1-AAs in ACS group and SAP group were significantly higher than those in control group,the positive rate of AT1-AAs in ACS group was significantly higher than that in SAP group,and there were statistical differences (P ＜ 0.01).The MCP-1 and hs-CRP levels in ACS group and SAP group were significantly higher than those in control group,the MCP-1 and hs-CRP levels in ACS group were significantly higher than those in SAP group,and there were statistical differences (P ＜ 0.01).The MCP-1 and hs-CRP levels in AT1-AAs positive patients in ACS group and SAP group were significantly higher than those in AT1-AAs negative patients,and there were statistical differences (P ＜0.01).Conclusions AT1-AAs may play an important role in the pathogenesis of ACS.Inducing the expression of inflammatory factor through AT1-AAs maybe an important mechanism for plaque instability.
