Correctness by Construction for Pairwise Sequence Alignment Algorithm in Bio-Sequence

Pairwise sequence alignment is a classical problem in bioinformatics, aiming at finding the similarity between two sequences, which is important for discovering functional, structural and evolutionary information in biological sequences. More algorithms have been developed for the sequence alignment problem. There is no formal development process for the existing pairwise sequence algorithms and leads to the low trustworthiness of those algorithms. In addition, the application of formal methods in the field of bioinformatics algorithm development is rarely seen. In this paper, we use a formal method PAR to construct a pairwise sequence algorithm, analyze the essence of the pairwise sequence alignment problem, construct the Apla algorithm program by stepwise refinement, and further verify its correctness. Finally a highly reliable and executable pairwise sequence alignment algorithm program is generated from Apla program via PAR platform. The formal construction process ensures the reliability of algorithm, and also demonstrates the algorithm design idea clearly, which makes the originally difficult algorithm design process easier. The successful practice of this method on the pairwise sequence alignment problem in biological sequence analysis can provide a reference for the construction of highly reliable algorithms in complex bioinformatics from both methodological and practical aspects

No-Regret Learning in Two-Echelon Supply Chain with Unknown Demand Distribution

Supply chain management (SCM) has been recognized as an important discipline with applications to many industries, where the two-echelon stochastic inventory model, involving one downstream retailer and one upstream supplier, plays a fundamental role for developing firms' SCM strategies. In this work, we aim at designing online learning algorithms for this problem with an unknown demand distribution, which brings distinct features as compared to classic online optimization problems. Specifically, we consider the two-echelon supply chain model introduced in [Cachon and Zipkin, 1999] under two different settings: the centralized setting, where a planner decides both agents' strategy simultaneously, and the decentralized setting, where two agents decide their strategy independently and selfishly. We design algorithms that achieve favorable guarantees for both regret and convergence to the optimal inventory decision in both settings, and additionally for individual regret in the decentralized setting. Our algorithms are based on Online Gradient Descent and Online Newton Step, together with several new ingredients specifically designed for our problem. We also implement our algorithms and show their empirical effectiveness

Discrepancy-Guided Reconstruction Learning for Image Forgery Detection

In this paper, we propose a novel image forgery detection paradigm for boosting the model learning capacity on both forgery-sensitive and genuine compact visual patterns. Compared to the existing methods that only focus on the discrepant-specific patterns (\eg, noises, textures, and frequencies), our method has a greater generalization. Specifically, we first propose a Discrepancy-Guided Encoder (DisGE) to extract forgery-sensitive visual patterns. DisGE consists of two branches, where the mainstream backbone branch is used to extract general semantic features, and the accessorial discrepant external attention branch is used to extract explicit forgery cues. Besides, a Double-Head Reconstruction (DouHR) module is proposed to enhance genuine compact visual patterns in different granular spaces. Under DouHR, we further introduce a Discrepancy-Aggregation Detector (DisAD) to aggregate these genuine compact visual patterns, such that the forgery detection capability on unknown patterns can be improved. Extensive experimental results on four challenging datasets validate the effectiveness of our proposed method against state-of-the-art competitors.Comment: 9 pages, 5 figure

A Method for Bio-Sequence Analysis Algorithm Development Based on the PAR Platform

The problems of biological sequence analysis have great theoretical and practical value in modern bioinformatics. Numerous solving algorithms are used for these problems, and complex similarities and differences exist among these algorithms for the same problem, causing difficulty for researchers to select the appropriate one. To address this situation, combined with the formal partition-and-recur method, component technology, domain engineering, and generic programming, the paper presents a method for the development of a family of biological sequence analysis algorithms. It designs highly trustworthy reusable domain algorithm components and further assembles them to generate specifific biological sequence analysis algorithms. The experiment of the development of a dynamic programming based LCS algorithm family shows the proposed method enables the improvement of the reliability, understandability, and development efficiency of particular algorithms

Myocardial Stunning-Induced Left Ventricular Dyssynchrony On Gated Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging

Objectives Myocardial stunning provides additional nonperfusion markers of coronary artery disease (CAD), especially for severe multivessel CAD. The purpose of this study is to assess the influence of myocardial stunning to the changes of left ventricular mechanical dyssynchrony (LVMD) parameters between stress and rest gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Patients and methods A total of 113 consecutive patients (88 males and 25 females) who had undergone both stress and rest 99mTc-sestamibi gated SPECT MPI were retrospectively enrolled. Suspected or known patients with CAD were included if they had exercise stress MPI and moderate to severe myocardial ischemia. Segmental scores were summed for the three main coronary arteries according to standard myocardial perfusion territories, and then regional perfusion, wall motion, and wall thickening scores were measured. Myocardial stunning was defined as both ischemia and wall dysfunction within the same coronary artery territory. Patients were divided into the stunning group (n=58) and nonstunning group (n=55). Results There was no significant difference of LVMD parameters between stress and rest in the nonstunning group. In the stunning group, phase SD and phase histogram bandwidth of contraction were significantly larger during stress than during rest (15.05±10.70 vs. 13.23±9.01 and 46.07±34.29 vs. 41.02±32.16, PP\u3c0.05). Conclusion Both systolic and diastolic LVMD parameters deteriorate with myocardial stunning. This kind of change may have incremental values to diagnose CAD

PLM-ARG: antibiotic resistance gene identification using a pretrained protein language model

Motivation: Antibiotic resistance presents a formidable global challenge to public health and the environment. While considerable endeavors have been dedicated to identify antibiotic resistance genes (ARGs) for assessing the threat of antibiotic resistance, recent extensive investigations using metagenomic and metatranscriptomic approaches have unveiled a noteworthy concern. A significant fraction of proteins defies annotation through conventional sequence similarity-based methods, an issue that extends to ARGs, potentially leading to their under-recognition due to dissimilarities at the sequence level. Results: Herein, we proposed an Artificial Intelligence-powered ARG identification framework using a pretrained large protein language model, enabling ARG identification and resistance category classification simultaneously. The proposed PLM-ARG was developed based on the most comprehensive ARG and related resistance category information (>28K ARGs and associated 29 resistance categories), yielding Matthew’s correlation coefficients (MCCs) of 0.983 ± 0.001 by using a 5-fold cross-validation strategy. Furthermore, the PLM-ARG model was verified using an independent validation set and achieved an MCC of 0.838, outperforming other publicly available ARG prediction tools with an improvement range of 51.8%–107.9%. Moreover, the utility of the proposed PLM-ARG model was demonstrated by annotating resistance in the UniProt database and evaluating the impact of ARGs on the Earth's environmental microbiota. Availability and implementation: PLM-ARG is available for academic purposes at https://github.com/Junwu302/PLM-ARG, and a user-friendly webserver (http://www.unimd.org/PLM-ARG) is also provided