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Yvan Saeys

Publications and source records attributed to Yvan Saeys.

2 recordsLinked to original sources

SCORPIUS improves trajectory inference and identifies novel modules in dendritic cell development

1Recent advances in RNA sequencing enable the generation of genome-wide expression data at the single-cell level, opening up new avenues for transcriptomics and systems biology. A new application of single-cell whole-transcriptomics is the unbiased ordering of cells according to their progression along a dynamic process of interest. We introduce SCORPIUS, a method which can effectively reconstruct an ordering of individual cells without any prior information about the dynamic process. Comprehensive evaluation using ten scRNA-seq datasets shows that SCORPIUS consistently outperforms state-of-the-art techniques. We used SCORPIUS to generate novel hypotheses regarding dendritic cell development, which were subsequently validated in vivo. This work enables data-driven investigation and characterization of dynamic processes and lays the foundation for objective benchmarking of future trajectory inference methods.

Bioinformatics

The CARD-CC/Bcl10/paracaspase signaling complex is functionally conserved since the last common ancestor of planulozoa.

Type 1 paracaspases originated in the Ediacaran geological period before the last common ancestor of bilaterians and cnidarians (Planulozoa). Cnidarians have several paralog type 1 paracaspases, type 2 paracaspases, and a homolog of Bcl10. Notably in bilaterians, lineages like nematodes and insects lack Bcl10 whereas other lineages such as vertebrates, hemichordates, annelids and mollusks have a Bcl10 homolog. A survey of invertebrate CARD-coiled-coil (CC) domain homologs of CARMA/CARD9 revealed such homologs only in species with Bcl10, indicating an ancient co-evolution of the entire CARD-CC/Bcl10/MALT1-like paracaspase (CBM) complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were found in invertebrate organisms with CARD-CC/Bcl10, indicating that this pathway might be the original user of the CBM complex. We also established that the downstream signaling proteins TRAF2 and TRAF6 are functionally conserved in Cnidaria. There also seems to be a correlation where invertebrates with CARD-CC and Bcl10 have type 1 paracaspases which are more similar to the paracaspases found in vertebrates. A proposed evolutionary scenario includes at least two ancestral type 1 paracaspase paralogs in the planulozoan last common ancestor, where at least one paralog usually is dependent on CARD-CC/Bcl10 for its function. Functional analyses of invertebrate type 1 paracaspases and Bcl10 homologs support this scenario and indicate an ancient origin of the CARD-CC/Bcl10/paracaspase signaling complex. Results from cnidarians, nematodes and mice also suggest an ancient neuronal role for the type 1 paracaspases.

Evolutionary Biology