Advances in chromatin mapping have exposed the complex chromatin hierarchical organization in mammals, including topologically associating domains (TADs) and their substructures, yet the functional implications of this hierarchy in gene regulation and disease progression are not fully elucidated. Our study delves into the phenomenon of shared TAD boundaries, which are pivotal in maintaining the hierarchical chromatin structure and regulating gene activity. By integrating high-resolution Hi-C data, chromatin accessibility, and DNA double-strand breaks (DSBs) data from various cell lines, we systematically explore the complex regulatory landscape at high-level TAD boundaries. Our findings indicate that these boundaries are not only key architectural elements but also vibrant hubs, enriched with functionally crucial genes and complex transcription factor binding site-clustered regions. Moreover, they exhibit a pronounced enrichment of DSBs, suggesting a nuanced interplay between transcriptional regulation and genomic stability. Our research provides novel insights into the intricate relationship between the 3D genome structure, gene regulation, and DNA repair mechanisms, highlighting the role of shared TAD boundaries in maintaining genomic integrity and resilience against perturbations. The implications of our findings extend to understanding the complexities of genomic diseases and open new avenues for therapeutic interventions targeting the structural and functional integrity of TAD boundaries.

Abstract Nested named entity recognition (NNER) aims to identify potentially overlapping named entities. Sequence labeling method and span-based method are two commonly used methods in nested named entity recognition. However, the linear structure of sequence labeling method results in relatively poor performance, and span-based method requires traversing all spans, which brings very high time complexity. All of them fail to effectively leverage the positional dependencies between internal and external entities. In order to improve these issues, this paper proposed a nested entity recognition method based on Multidimensional Features and Fuzzy Localization (MFFL). Firstly, this method adopted the shared encoding that fused three features of characters, words, and parts of speech to obtain a multidimensional feature vector representation of the text and obtained rich semantic information in the text. Secondly, we proposed to use the fuzzy localization to assist the model in pinpointing the potential locations of entities. Finally, in the entity classification, it used a window to expand the sub-sequence and enumerate possible candidate entities and predicted the classification labels of these candidate entities. In order to alleviate the problem of error propagation and effectively learn the correlation between fuzzy localization and classification labels, we adopted multi-task learning strategy. This paper conducted several experiments on two public datasets. The experimental results showed that the proposed method achieves ideal results in both nested entity recognition and non-nested entity recognition tasks, and significantly reduced the time complexity of nested entity recognition.