Alessandro Vinceti

Motivation Binary (or boolean) matrices provide a common effective data representation adopted in several domains of computational biology, especially for investigating cancer and other human diseases. For instance, they are used to summarise genetic aberrations—copy number alterations or mutations—observed in cancer patient cohorts, effectively highlighting combinatorial relations among them. One of these is the tendency […]

A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes arising from copy-number-amplified genomics regions. To solve this issue, we previously developed CRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing […]

Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity1. The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC). Using spatially resolved paired whole-genome and transcriptome sequencing, […]

Pooled genome-wide CRISPR-Cas9 screens are furthering our mechanistic understanding of human biology and have allowed us to identify new oncology therapeutic targets. Scale-limited CRISPR-Cas9 screens—typically employing guide RNA libraries targeting subsets of functionally related genes, biological pathways, or portions of the druggable genome—constitute an optimal setting for investigating narrow hypotheses and are easier to execute […]

Background CRISPR-Cas9 genome-wide screens are being increasingly performed, allowing systematic explorations of cancer dependencies at unprecedented accuracy and scale. One of the major computational challenges when analysing data derived from such screens is to identify genes that are essential for cell survival invariantly across tissues, conditions, and genomic-contexts (core-fitness genes), and to distinguish them from […]