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Timmers, P.

Publications and source records attributed to Timmers, P..

2 recordsLinked to original sources

Identifying eukaryotes in drinking water metagenomes and factors influencing their biogeography.

The biogeography of eukaryotes in drinking water systems is poorly understood relative to prokaryotes or viruses. A common challenge with studying complex eukaryotic communities from natural and engineered systems is that the metagenomic analysis workflows are currently not as mature as those that focus on prokaryotes or even viruses. In this study, we benchmarked different strategies to recover eukaryotic sequences and genomes from metagenomic data and applied the best-performing workflow to explore eukaryotic communities present in drinking water distribution systems (DWDSs). We developed an ensemble approach that exploits k-mer and reference-based strategies to improve eukaryotic sequence identification from metagenomes and identified MetaBAT2 as the best performing binning approach for clustering of eukaryotic sequences. Applying this workflow on the DWDSs metagenomes showed that eukaryotic sequences typically constituted a small proportion (i.e., <1%) of the overall metagenomic data. Eukaryotic sequences showed higher relative abundances in surface water-fed and chlorine disinfected systems. Further, the alpha and beta-diversity of eukaryotes were correlated with prokaryotic and viral communities. Finally, a co-occurrence analysis highlighted clusters of eukaryotes whose presence and abundance in DWDSs is affected by disinfection strategies, climate conditions, and source water types. SynopsisAfter benchmarking tools and developing a dedicated consensus workflow for eukaryotic sequence detection in metagenomes, the experimental, environmental, and engineering factors affecting their biogeography in drinking water distribution systems were investigated Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/518372v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1ae8423org.highwire.dtl.DTLVardef@653471org.highwire.dtl.DTLVardef@5606b7org.highwire.dtl.DTLVardef@1d30cde_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Comparative analysis of mammal genomes unveils key genomic variability for human lifespan.

Mammals vary 100-fold in their maximum lifespan. This enormous variation is the result of the adaptations of each species to their own biological trade-offs and ecological conditions. Comparative genomics studies have demonstrated that the genomic factors underlying the lifespans of species and the longevity of individuals are shared across the tree of life. Here, we set out to compare protein-coding regions across the mammalian phylogeny, aiming to detect individual amino acid changes shared by the most long-lived mammal species and genes whose rates of protein evolution correlate with longevity. We discovered a total of 2,737 amino acid changes in 2,004 genes that distinguish long- and short-lived mammals, significantly more than expected by chance (p=0.003). The detected genes belong to pathways involved in regulating lifespan, such as inflammatory response and hemostasis. Among them, a total 1,157 amino acids, located in 996 different genes, showed a significant association with maximum lifespan in a phylogenetically controlled test. Interestingly, most of the detected amino acids positions do not vary in extant human populations (>81.2%) or have allele frequencies below 1% (99.78%), Consequently, almost none could have been detected by Genome-Wide Association Studies (GWAS). Additionally, we identified four more genes whose rate of protein evolution correlated with longevity in mammals. Crucially, SNPs located in the detected genes explain a larger fraction of human lifespan heritability than expected by chance, successfully demonstrating for the first time that comparative genomics can be used to enhance the interpretation of human GWAS. Finally, we show that the human longevity-associated proteins coded by the detected genes are significantly more stable than the orthologous proteins from short-lived mammals, strongly suggesting that general protein stability is linked to increased lifespan.

genomics↗