Analysis of single-cell data from tumors

Material for the OLISSIPO workshop on April 4th, 2023.

Thank you Susana Vinga for inviting me and Sara Tanqueiro and the OLISSIPO team for organizing! I had a wonderful time interacting with the local community and I look forward to more meetings in the future.


Title:

Analysis of single-cell data from tumors

Abstract:

Cancer is an evolutionary process in which cells acquire mutations that may lead to their uncontrolled proliferation. As a result of spatial constraints, competitiveness between cancer cells and interactions with the immune system, tumors exhibit significant heterogeneity within and across patients. The advent of next-generation sequencing and recent extensions to single-cell level assays at high throughput has enabled practitioners to characterize this heterogeneity with unprecedented detail. Sequencing genomes and transcriptomes of thousands of single cells individually has shed light on mechanisms of tumor progression, metastasis and treatment resistance. In this course, we will provide an overview of how sequencing data can be used to unravel intra-tumor heterogeneity, and highlight the computational methods that transform those data into biological insights. In the first part, we will overview scDNA and scRNA technologies and the questions they allow us to answer in the context of tumor evolution, with a focus on single-nucleotide variant and copy number calling, and event history reconstruction. In the second session, we will focus on statistical methods and their application to the analysis of these data. In the hands-on session, we will analyse scDNA and scRNA data using recent tools for clustering noisy mutational profiles and identifying hierarchical signatures of gene expression. The practical session will use Python. A laptop with internet access is required for the practical session, and basic familiarity with Python is beneficial. All materials will be made available at https://pedrofale.github.io.

Programme:

Bio:

Pedro Falé Ferreira is a PhD student at the Computational Biology Group at the Department of Biosystems Science and Engineering of ETH Zürich in Basel, Switzerland. He is supervised by Prof. Niko Beerenwinkel and Dr. Jack Kuipers. He develops computational methods to analyse high-throughput single-cell sequencing data and reconstruct the evolutionary history of tumors and has presented his work in several international venues. He obtained his MSc. from Instituto Superior Técnico in Lisbon, Portugal in 2018 under the supervision of Prof. Susana Vinga and Prof. Alexandra M. Carvalho. More information about his research is available at https://pedrofale.github.io.

Material:

Acknowledgements

Thank you to Nico Borgsmüller for helping with BnpC for the mutation clustering hands-on session.