bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2023‒07‒09
four papers selected by
Lara Paracchini
Humanitas Research

  1. Nat Biotechnol. 2023 Jul 06.
      Characterization of somatic mutations at single-cell resolution is essential to study cancer evolution, clonal mosaicism and cell plasticity. Here, we describe SComatic, an algorithm designed for the detection of somatic mutations in single-cell transcriptomic and ATAC-seq (assay for transposase-accessible chromatin sequence) data sets directly without requiring matched bulk or single-cell DNA sequencing data. SComatic distinguishes somatic mutations from polymorphisms, RNA-editing events and artefacts using filters and statistical tests parameterized on non-neoplastic samples. Using >2.6 million single cells from 688 single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) data sets spanning cancer and non-neoplastic samples, we show that SComatic detects mutations in single cells accurately, even in differentiated cells from polyclonal tissues that are not amenable to mutation detection using existing methods. Validated against matched genome sequencing and scRNA-seq data, SComatic achieves F1 scores between 0.6 and 0.7 across diverse data sets, in comparison to 0.2-0.4 for the second-best performing method. In summary, SComatic permits de novo mutational signature analysis, and the study of clonal heterogeneity and mutational burdens at single-cell resolution.
  2. Nature. 2023 Jul 05.
    Keywords:  Cancer; Cosmology; Evolution; Genetics; Synthetic biology
  3. Lung. 2023 Jul 05.
      INTRODUCTION: Maximising alternative sample types for genomics in advanced lung cancer is important because bronchoscopic samples may sometimes be insufficient for this purpose. Further, the clinical applications of comprehensive molecular analysis such as whole genome sequencing (WGS) are rapidly developing. Diff-Quik cytology smears from EBUS TBNA is an alternative source of DNA, but its feasibility for WGS has not been previously demonstrated.METHODS: Diff-Quik smears were collected along with research cell pellets.
    RESULTS: Tumour content of smears were compared to research cell pellets from 42 patients, which showed good correlation (Spearman correlation 0.85, P < 0.0001). A subset of eight smears underwent WGS, which presented similar mutation profiles to WGS of the matched cell pellet. DNA yield was predicted using a regression equation of the smears cytology features, which correctly predicted DNA yield > 1500 ng in 7 out of 8 smears.
    CONCLUSIONS: WGS of commonly collected Diff-Quik slides is feasible and their DNA yield can be predicted.
    Keywords:  Cytology; Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS TBNA); Lung cancer; Molecular diagnostics; Whole genome sequencing
  4. Lancet Oncol. 2023 Jul;pii: S1470-2045(23)00295-4. [Epub ahead of print]24(7): 709