Biology subjects

Moerman, T.

Publications and source records attributed to Moerman, T..

3 recordsLinked to original sources

bioRxiv2020

Spatially-Aware Clustering of Ion Images in Mass Spectrometry Imaging Data Using Deep Learning

Computational analysis is crucial to capitalize on the wealth of spatio-molecular information generated by mass spectrometry imaging (MSI) experiments. Currently, the spatial information available in MSI data is often under-utilized, due to the challenges of in-depth spatial pattern extraction. The advent of deep learning has greatly facilitated such complex spatial analysis. In this work, we use a pre-trained neural network to extract high-level features from ion images in MSI data, and test whether this improves downstream data analysis. The resulting neural network interpretation of ion images, coined neural ion images, are used to cluster ion images based on spatial expressions. We evaluate the impact of neural ion images on two ion image clustering pipelines, namely DBSCAN clustering, combined with UMAP-based dimensionality reduction, and k-means clustering. In both pipelines, we compare regular and neural ion images from two different MSI datasets. All tested pipelines could extract underlying spatial patterns, but the neural network-based pipelines provided better assignment of ion images, with more fine-grained clusters, and greater consistency in the spatial structures assigned to individual clusters. Additionally, we introduce the Relative Isotope Ratio metric to quantitatively evaluate clustering quality. The resulting scores show that isotopical m/z values are more often clustered together in the neural network-based pipeline, indicating improved clustering outcomes. The usefulness of neural ion images extends beyond clustering towards a generic framework to incorporate spatial information into any MSI-focused machine learning pipeline, both supervised and unsupervised.

bioinformatics↗

bioRxiv2017

A single-cell catalogue of regulatory states in the ageing Drosophila brain

The diversity of cell types and regulatory states in the brain, and how these change during ageing, remains largely unknown. Here, we present a single-cell transcriptome catalogue of the entire adult Drosophila melanogaster brain sampled across its lifespan. Both neurons and glia age through a process of \"regulatory erosion\", characterized by a strong decline of RNA content, and accompanied by increasing transcriptional and chromatin noise. We identify more than 50 cell types by specific transcription factors and their downstream gene regulatory networks. In addition to neurotransmitter types and neuroblast lineages, we find a novel neuronal cell state driven by datilografo and prospero. This state relates to neuronal birth order, the metabolic profile, and the activity of a neuron. Our single-cell brain catalogue reveals extensive regulatory heterogeneity linked to ageing and brain function and will serve as a reference for future studies of genetic variation and disease mutations.

genomics↗

bioRxiv2017

SCENIC: Single-Cell Regulatory Network Inference And Clustering

Single-cell RNA-seq allows building cell atlases of any given tissue and infer the dynamics of cellular state transitions during developmental or disease trajectories. Both the maintenance and transitions of cell states are encoded by regulatory programs in the genome sequence. However, this regulatory code has not yet been exploited to guide the identification of cellular states from single-cell RNA-seq data. Here we describe a computational resource, called SCENIC (Single Cell rEgulatory Network Inference and Clustering), for the simultaneous reconstruction of gene regulatory networks (GRNs) and the identification of stable cell states, using single-cell RNA-seq data. SCENIC outperforms existing approaches at the level of cell clustering and transcription factor identification. Importantly, we show that cell state identification based on GRNs is robust towards batch-effects and technical-biases. We applied SCENIC to a compendium of single-cell data from the mouse and human brain and demonstrate that the proper combinations of transcription factors, target genes, enhancers, and cell types can be identified. Moreover, we used SCENIC to map the cell state landscape in melanoma and identified a gene regulatory network underlying a proliferative melanoma state driven by MITF and STAT and a contrasting network controlling an invasive state governed by NFATC2 and NFIB. We further validated these predictions by showing that two transcription factors are predominantly expressed in early metastatic sentinel lymph nodes. In summary, SCENIC is the first method to analyze scRNA-seq data using a network-centric, rather than cell-centric approach. SCENIC is generic, easy to use, and flexible, and allows for the simultaneous tracing of genomic regulatory programs and the mapping of cellular identities emerging from these programs. Availability: SCENIC is available as an R workflow based on three new R/Bioconductor packages: GENIE3, RcisTarget and AUCell. As scalable alternative to GENIE3, we also provide GRNboost, paving the way towards the network analysis across millions of single cells.

bioinformatics↗