20 research outputs found
Integrated Molecular Characterization of Uterine Carcinosarcoma
SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Scarf-Akin Osteotomy Correction for Hallux Valgus: Short-term Results from a District General Hospital
Value of contrast-enhanced ultrasonography of the carotid artery for evaluating disease activity in Takayasu arteritis
Composition comparison of Zhejiang Longquan celadon and its imitation in Dapu kiln of Guangdong in the Ming Dynasty of China (1368–1644 CE) by LA-ICP-MS
Time delay between diagnosis and arthroscopic lavage in septic arthritis. Does it matter?
ONTD induces apoptosis of human hepatoma Bel-7402 cells via a MAPK-dependent mitochondrial pathway and the depletion of intracellular glutathione
A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida albicans morphological transition
10.1038/ismej.2007.76ISME Journal2127-3