Molecular recognition features (MoRFs) are short binding regions located in longer intrinsically disordered protein regions. Although these short regions lack a stable structure in the natural state, they readily undergo disorder-to-order transitions upon binding to their partner molecules. MoRFs play critical roles in the molecular interaction network of a cell, and are associated with many human genetic diseases. Therefore, identification of MoRFs is an important step in understanding functional aspects of these proteins and in finding applications in drug design.

The inner representation of deep neural networks (DNNs) is indecipherable, which makes it difficult to tune DNN models, control their training process, and interpret their outputs. In this paper, we propose a novel approach to investigate the inner representation of DNNs through topological data analysis (TDA). Persistent homology (PH), one of the outstanding methods in TDA, was employed for investigating the complexities of trained DNNs. We constructed clique complexes on trained DNNs and calculated the one-dimensional PH of DNNs. The PH reveals the combinational effects of multiple neurons in DNNs at different resolutions, which is difficult to be captured without using PH. Evaluations were conducted using fully connected networks (FCNs) and networks combining FCNs and convolutional neural networks (CNNs) trained on the MNIST and CIFAR-10 data sets. Evaluation results demonstrate that the PH of DNNs reflects both the excess of neurons and problem difficulty, making PH one of the prominent methods for investigating the inner representation of DNNs.

Multiple sequence alignment (MSA) is a useful tool in bioinformatics. Although many MSA algorithms have been developed, there is still room for improvement in accuracy and speed. In the alignment of a family of protein sequences, global MSA algorithms perform better than local ones in many cases, while local ones perform better than global ones when some sequences have long insertions or deletions (indels) relative to others. Many recent leading MSA algorithms have incorporated pairwise alignment information obtained from a mixture of sources into their scoring system to improve accuracy of alignment containing long indels. We propose a novel group-to-group sequence alignment algorithm that uses a piecewise linear gap cost. We developed a program called PRIME, which employs our proposed algorithm to optimize the well-defined sum-of-pairs score. PRIME stands for Profile-based Randomized Iteration MEthod. We evaluated PRIME and some recent MSA programs using BAliBASE version 3.0 and PREFAB version 4.0 benchmarks. The results of benchmark tests showed that PRIME can construct accurate alignments comparable to the most accurate programs currently available, including L-INS-i of MAFFT, ProbCons, and T-Coffee. PRIME enables users to construct accurate alignments without having to employ pairwise alignment information. PRIME is available at http://prime.cbrc.jp/.

Yuxiang Zhang, Jing Chen, Junjie Wang, Yaxin Liu, Cheng Yang, Chufan Shi, Xinyu Zhu, Zihao Lin, Hanwen Wan, Yujiu Yang, Tetsuya Sakai, Tian Feng, Hayato Yamana. Proceedings of the 2024 Conference on Empirical Methods in Natural Language Processing. 2024.