TRGT-denovo: accurate detection of de novo tandem repeat mutations.

Motivation: Identifying de novo tandem repeat (TR) mutations on a genome-wide scale is essential for understanding genetic variability and its implications in rare diseases. While PacBio HiFi sequencing data enhances the accessibility of the genome's TR regions for genotyping, simple de novo calling strategies often generate an excess of likely false positives, which can obscure true positive findings, particularly as the number of surveyed genomic regions increases. Results: We developed TRGT-denovo, a computational method designed to accurately identify all types of de novo TR mutations-including expansions, contractions, and compositional changes-within family trios. TRGT-denovo directly interrogates read evidence, allowing for the detection of subtle variations often overlooked in variant call format (VCF) files. TRGT-denovo improves the precision and specificity of de novo mutation (DNM) identification, reducing the number of de novo candidates by an order of magnitude compared to genotype-based approaches. In our experiments involving eight rare disease trios previously studiedTRGT-denovo correctly reclassified all false positive DNM candidates as true negatives. Using an expanded repeat catalog, it identified new candidates, of which 95% (19/20) were experimentally validated, demonstrating its effectiveness in minimizing likely false positives while maintaining high sensitivity for true discoveries. Availability and implementation: Built in Rust, TRGT-denovo is available as source code and a pre-compiled Linux binary along with a user guide at: https://github.com/PacificBiosciences/trgt-denovo.

[Diaskintest for tuberculosis in children and adolescents].

To study whether Diaskintest might be used as a criterion for the activity of local tuberculous changes in children and adolescents, the authors examined three groups of patients aged 0 to 17 years: 1) 20 patients with new-onset tuberculosis in the progression phase; 2) 25 patients with new-onset tuberculosis in the regression phase with the signs of consolidation and calcification; 3) 18 tuberculosis dispensary Group IIIB patients who received the basic course of therapy and had residual posttuberculous changes as calcinates and compact foci. Group 3 was found to greatly differ from Groups 1 and 2 in the lower rates of positive reactions, the higher rate of negative reactions, and smaller papulae while the Mantoux test with 2 TE indicated that in Group 3, the papulae were smaller than those in Group 2. Responses to the Diaskintest test versus the Mantoux 2TE test were significantly more pronounced in patients with progressive tuberculosis and less marked in dispensary Group IIB patients who received the basic course of antituberculous therapy. Diaskintest was ascertained to be used in the complex examination of children and adolescents as a criterion for the activity of tuberculous changes in order to choose the tactics of treatment and follow-up of children and adolescents. The application of Diaskintest will allow more objective formation of dispensary Group IIIA of children served by a local phthisiatrician.