05/2018 - Quantification of subclonal selection in cancer from bulk sequencing data
Subclonal architectures are prevalent across cancer types. However, the temporal evolutionary dynamics that produce tumor subclones remain unknown. Here we measure clone dynamics in human cancers by using computational modeling of subclonal selection and theoretical population genetics applied to high-throughput sequencing data. Our method determined the detectable subclonal architecture of tumor samples and simultaneously measured […]
05/2018 - On the role of statistics in the era of big data: A call for a debate
While discussing the plenary talk of Dunson (2016) at the 48th Scientific Meeting of the Italian Statistical Society, I formulated a few general questions on the role of statistics in the era of big data which stimulated an interesting debate. They are reported here with the aim of engaging a larger audience on an issue […]
04/2018 - Structural rearrangements of the RNA polymerase III machinery during tRNA transcription initiation
RNA polymerase III catalyses the synthesis of tRNAs in eukaryotic organisms. Through combined biochemical and structural characterisation, multiple auxiliary factors have been identified alongside RNA Polymerase III as critical in both facilitating and regulating transcription. Together, this machinery forms dynamic multi-protein complexes at tRNA genes which are required for polymerase recruitment, DNA opening and initiation […]
02/2018 - Patient-derived organoids model treatment response of metastatic gastrointestinal cancers
Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree […]