
Cell Reports, Год журнала: 2024, Номер 43(11), С. 114897 - 114897
Опубликована: Окт. 19, 2024
Язык: Английский
Cell Reports, Год журнала: 2024, Номер 43(11), С. 114897 - 114897
Опубликована: Окт. 19, 2024
Язык: Английский
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Дек. 25, 2024
Despite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (TF) binding at context-specific cREs remain elusive. We introduce ChromBPNet, a deep learning DNA model base-resolution profiles detects, learns deconvolves assay-specific enzyme biases from regulatory determinants accessibility, enabling robust discovery compact TF motif lexicons, cooperative precision footprints assays sequencing depths. Extensive benchmarks show despite its lightweight design, is competitive much larger contemporary models predicting variant effects on pioneer reporter activity cell ancestry, while providing interpretation disrupted syntax. ChromBPNet also helps prioritize interpret influence complex traits rare diseases, thereby powerful lens to decode variation.
Язык: Английский
Процитировано
11ACS Synthetic Biology, Год журнала: 2025, Номер unknown
Опубликована: Май 22, 2025
CRISPR technology has revolutionized genome editing by enabling precise, permanent modifications to genetic material. To circumvent the irreversible alterations associated with traditional methods and facilitate research on both essential nonessential genes, interference or inhibition (CRISPRi) activation (CRISPRa) were developed. The gene-silencing approach leverages an inactivated Cas effector protein paired guide RNA obstruct transcription initiation elongation, while gene-activation exploits programmability of activate gene expression. Recent advances in CRISPRi technology, combination other technologies (e.g., biosensing, sequencing), have significantly expanded its applications, allowing for genome-wide high-throughput screening (HTS) identify determinants phenotypes. These strategies been applied biomedicine, industry, basic research. This review explores regulation mechanisms, offers overview workflow CRISPR-based screens, highlights superior suitability HTS across biomedical industrial applications. Finally, we discuss limitations current CRISPRi/a envision future directions CRISPR-mediated research, considering potential broader application diverse fields.
Язык: Английский
Процитировано
0Stem Cell Reports, Год журнала: 2025, Номер unknown, С. 102511 - 102511
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
0Cell Reports, Год журнала: 2024, Номер 43(11), С. 114853 - 114853
Опубликована: Окт. 19, 2024
Процитировано
2medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июль 24, 2024
In a patient with permanent neonatal syndromic diabetes clinically similar to cases ONECUT1 biallelic mutations, we identified disease-causing deletion located upstream of ONECUT1. Through genetic, genomic and functional studies crucial regulatory region acting as an enhancer specifically during pancreatic development. This contains low-frequency variant showing strong association type 2 other glycemic traits, thus extending the contribution this common forms diabetes. Clinical relevance is provided by experimentally tailored therapy options for patients carrying coding or mutations.
Язык: Английский
Процитировано
1Cell Reports, Год журнала: 2024, Номер 43(11), С. 114897 - 114897
Опубликована: Окт. 19, 2024
Язык: Английский
Процитировано
0