Biology subjects

Marot-Lassauzaie, V.

Publications and source records attributed to Marot-Lassauzaie, V..

3 recordsLinked to original sources

bioRxiv2024

Identifying cancer cells from calling single-nucleotide variants in scRNA-seq data

Single cell RNA sequencing (scRNA-seq) data is widely used to study cancer cell states and their heterogeneity. However, the tumour microenvironment is usually a mixture of healthy and cancerous cells and it can be difficult to fully separate these two populations based on transcriptomics alone. If available, somatic single nucleotide variants (SNVs) observed in the scRNA-seq data could be used to identify the cancer population. However, calling somatic SNVs in scRNA-seq data is a challenging task, as most variants seen in the short read data are not somatic, but can instead be germline variants, RNA edits or transcription, sequencing or processing errors. Additionally, only variants present in actively transcribed regions for each individual cell will be seen in the data. To address these challenges, we develop CCLONE (Cancer Cell Labelling On Noisy Expression), an interpretable tool adapted to handle the uncertainty and sparsity of SNVs called from scRNA-seq data. CCLONE jointly identifies cancer clonal populations, and their associated variants. We apply CCLONE on two acute myeloid leukaemia datasets and one lung adenocarcinoma dataset and show that CCLONE captures both genetic clones and somatic events for multiple patients. These results show how CCLONE can be used to gather insight into the course of the disease and the origin of cancer cells in scRNA-seq data.

bioinformatics↗

bioRxiv2022

Towards reliable quantification of cell state velocities

A few years ago, it was proposed to use the simultaneous quantification of unspliced and spliced messenger RNA (mRNA) to add a temporal dimension to high-throughput snapshots of single cell RNA sequencing data. This concept can yield additional insight into the transcriptional dynamics of the biological systems under study. However, current methods for inferring cell state velocities from such data (known as RNA velocities) are afflicted by several theoretical and computational problems, hindering realistic and reliable velocity estimation. We discuss these issues and propose new solutions for addressing some of the current challenges in consistency of data processing, velocity inference and visualisation. We translate our computational conclusion in two velocity analysis tools: one detailed method{kappa} -velo and one heuristic method eco-velo. Author summarySingle cell transcriptomics has been used to study dynamical biological processes such as cell differentiation or disease progression. An ideal study of these systems would track individual cells in time but this is not directly feasible since cells are destroyed as part of the sequencing protocol. Because of asynchronous progression of cells, single cell snapshot datasets often capture cells at different stages of progression. The challenge is to infer both the overall direction of progression (pseudotime) as well as single cell specific variations in the progression. Computational methods development for inference of the overall direction are well advanced but attempts to address the single cell level variations of the dynamics are newer. La Manno et al. [1] proposed that simultaneous measurement of abundances of new (unspliced) and older (spliced) mRNA in the same single cell adds a temporal dimension to the data which can be used to infer the time derivative of single cells progression through the dynamical process. State-of-the-art methods for inference of cell state velocities from RNA-seq data (also known as RNA velocity) have multiple unaddressed issues. In this manuscript, we discuss these issues and propose new solutions. In previous works, agreement of RNA velocity estimations with pseudotime has been used as validation. We show that this in itself is not proof that the method works reliably and the overall direction of progression has to be distinguished from individual cells behaviour. We propose two new methods (one detailed and one cost efficient heuristic) for estimation and visualisation of RNA velocities and show that our methods faithfully capture the single-cell variances and overall trend on simulation. We further apply the methods to a dataset of developing mouse pancreas and show how the method can help us gain biological insight from real data.

bioinformatics↗

bioRxiv2019

Spectrum of protein localization in proteomes captures evolutionary relation between species

The native subcellular localization or cellular compartment of a protein is the one in which it acts most often; it is one aspect of protein function. Do ten eukaryotic model organisms differ in their location spectrum, i.e. the fraction of its proteome in each of its seven major compartments? As experimental annotations of locations remain biased and incomplete, we need prediction methods to answer this question. To gauge the bias of prediction methods, we merged all available experimental annotations for the human proteome. In doing so, we found important values in both Swiss-Prot and the Human Protein Atlas (HPA). After systematic bias corrections, the complete but faulty prediction methods appeared to be more appropriate to compare location spectra between species than the incomplete more accurate experimental data. This work compared the location spectra for ten eukaryotes: Homo sapiens, Gorilla gorilla, Pan troglodytes, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Anopheles gambiae, Caenorhabitis elegans, Saccharomyces cerevisiae and Schizosaccharomyces pombe. Overall, the predicted location spectra were similar. However, the detailed differences were significant enough to plot trees and 2D (PCA) maps relating the ten organisms using a simple Euclidean distance in seven states, corresponding to the seven studied localization classes. The relations based on the simple predicted location spectra captured aspects of cross-species comparisons usually revealed only by much more detailed evolutionary comparisons.

bioinformatics↗