Nov 2025· JACS Au· Vol 5, pp. 5676 - 5689· 4 citations· ⚡ 1 influential· 75 references
Medicine
Abstract
Targeted covalent drugs have demonstrated remarkable potential in disease treatment over the past decades. However, existing methods for covalent drug design are often limited to serine and cysteine, ignoring other potentially ligandable binding sites. Statistical analyses indicate that over 95% of binding pockets contain covalent-binding residues, suggesting that all ligands that targeting these pockets possess the potential to be modified into covalent ligands. To achieve this goal, we introduced CovalentLab, an interactive computational platform that integrates ligand-based and warhead-based strategies into a unified workflow for the rational design of covalent ligands. Leveraging a covalent binding site prediction model constructed on ESM-2 with LoRA fine-tuning, CovalentLab enables the prediction and ranking of nine classes of covalent-binding residues in proteins according to their reactivity and facilitates systematic warhead attachment to ligands using 210 electrophilic groups or user-defined warheads. Using this platform, a comprehensive library of more than 100,000 covalent molecules across 95 targets was generated. Notably, CovalentLab has been successfully applied to various essential real-world targets, identifying wet-laboratory-validated bioactive compounds ranging from TRK orthosteric inhibitors to GAC allosteric inhibitors. By bridging gaps in covalent drug discovery, CovalentLab offers a versatile, publicly accessible resource to expand the druggable targets and accelerate the development of targeted covalent therapies.
Agile - denoting "the quality of being agile, readiness for motion, nimbleness, activity, dexterity in motion" - software development methods are attempting to offer an answer to the eager business community asking for lighter weight along with faster and nimbler software development processes. This is especially the case with the rapidly growing and volatile Internet software industry as well as for the emerging mobile application environment. The new agile methods have evoked substantial amount of literature and debates. However, academic research on the subject is still scarce, as most of existing publications are written by practitioners or consultants. The aim of this publication is to begin filling this gap by systematically reviewing the existing literature on agile software development methodologies. This publication has three purposes. First, it proposes a definition and a classification of agile software development approaches. Second, it analyses ten software development methods that can be characterized as being "agile" against the defined criterion. Third, it compares these methods and highlights their similarities and differences. Based on this analysis, future research needs are identified and discussed.
P. Abrahamsson, O. Salo, Jussi Ronkainen et al.· arXiv.org· 728 citations· ⚡54
Context: Software startups are newly created companies with no operating history and fast in producing cutting-edge technologies. These companies develop software under highly uncertain conditions, tackling fast-growing markets under severe lack of resources. Therefore, software startups present a unique combination of characteristics which pose several challenges to software development activities. Objective: This study aims to structure and analyze the literature on software development in startup companies, determining thereby the potential for technology transfer and identifying software development work practices reported by practitioners and researchers. Method: We conducted a systematic mapping study, developing a classification schema, ranking the selected primary studies according their rigor and relevance, and analyzing reported software development work practices in startups. Results: A total of 43 primary studies were identified and mapped, synthesizing the available evidence on software development in startups. Only 16 studies are entirely dedicated to software development in startups, of which 10 result in a weak contribution (advice and implications (6); lesson learned (3); tool (1)). Nineteen studies focus on managerial and organizational factors. Moreover, only 9 studies exhibit high scientific rigor and relevance. From the reviewed primary studies, 213 software engineering work practices were extracted, categorized and analyzed. Conclusion: This mapping study provides the first systematic exploration of the state-of-art on software startup research. The existing body of knowledge is limited to a few high quality studies. Furthermore, the results indicate that software engineering work practices are chosen opportunistically, adapted and configured to provide value under the constrains imposed by the startup context.
Nicolò Paternoster, Carmine Giardino, M. Unterkalmsteiner et al.· Information and Software Tec...· 394 citations· ⚡54
What if pathology foundation models could do more with less? GigaPath-Flash and GigaTIME-Flash cut computational demands while maintaining strong performance, opening the door to larger studies and broader exploration. The post GigaPath-Flash and GigaTIME-Flash: Toward population-scale discovery with efficient pathology foundation models appeared first on Microsoft Research.
Through research and entrepreneurship, Professor Devavrat Shah is helping to design methods that can handle constant decision-making using limited computational resources.
