Aug 2026· ACS Synthetic Biology· 0 citations· 34 references
TL;DR
DeepCRISPR-Typer is presented, a comprehensive computational framework integrating a large protein language model (TEMC-Cas), a deep sequence feature extractor (CRISPR-RepTyper), and an adaptive targeted HMM profiling strategy that significantly reduces computational overhead by dynamically invoking subtype-specific HMM subsets.
Abstract
Accurate identification and classification of CRISPR-Cas systems are crucial for understanding microbial immune mechanisms and developing novel genome-editing tools. However, traditional homology-based mining methods face severe computational bottlenecks and assembly fragmentation challenges when processing massive metagenomic data. Here, we present DeepCRISPR-Typer, a comprehensive computational framework integrating a large protein language model (TEMC-Cas), a deep sequence feature extractor (CRISPR-RepTyper), and an adaptive targeted HMM profiling strategy. DeepCRISPR-Typer integrates array and Cas evidence and significantly reduces computational overhead by dynamically invoking subtype-specific HMM subsets. In metagenomic dataset evaluations, DeepCRISPR-Typer achieved a classification accuracy of 94.26% and demonstrated a significant acceleration of approximately 1 orders of magnitude compared to existing mainstream tools. This research provides a robust and scalable engine for metagenome-scale CRISPR system discovery, significantly expanding the mining toolbox for genome engineering applications.
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute adaptive immune systems in prokaryotes and have transformed life sciences, precision medicine, and synthetic biology as programmable genome-editing tools. Despite their broad utility, naturally occurring...
Lingwei She, Zeyu Liang, Qin Zou et al.· ACS Synthetic Biology· 2 citations
Five previously uncharacterized MG102-like Cas9d orthologs are identified that share the hallmark genomic, sequence, and structural features of type II-D Cas9 and establish compact MG102-like Cas9d orthologs as robust and specific genome editors and provide promising, single-AAV– compatible scaffolds for in vivo therap...
Qiaochu Wang, Ahmed Saleh, G. S. Rao et al.· bioRxiv· 0 citations
Abstract Summary CRISPR-Cas9 has become a widely used tool for genome editing. However, its off-target cleavage caused by partial sequence matches with guide RNAs (gRNAs) remains a critical limitation. Recently, abasic gRNAs (ØXØ) have been developed to enhance target specificity, but their effects vary depending on th...
Geun-Woo D. Kim, Dowoon Gu, Mingyo Park et al.· Bioinform.· 0 citations
Anti-CRISPR (Acr) proteins are natural inhibitors of CRISPR-Cas systems and are important regulators for controllable genome-editing applications. However, their computational identification remains challenging because Acrs are sequence-diverse, weakly conserved, and supported by limited labeled data. Here, we present...
K. Tan, Wei-Di Sun, M. Fullwood et al.· IEEE journal of biomedical a...· 0 citations
Accurate identification of CRISPR-Cas9 off-target sites is essential for the safety assessment of genome-editing-based therapies. While numerous in silico prediction tools have been developed, their comparative performance and practical utility in preclinical workflows remain incompletely defined. We performed a system...
M. M. Kaufmann, Maren Hackenberg, William Jobson Pargeter et al.· Human Gene Therapy· 0 citations
UCRISPRa achieved selective activation of olfr544 among more than a thousand homologous olfactory receptor genes in skeletal muscle cells, leading to enhanced mitochondrial biogenesis and broad potential for precise gene regulation and functional studies of complex macromolecular systems.
Smith Le, T. Thach· The FEBS Journal· 0 citations
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