Biology subjects

Rust, J.

Publications and source records attributed to Rust, J..

3 recordsLinked to original sources

bioRxiv2022

Global analysis of the yeast knock-out phenome

Genome-wide phenotypic screens in the budding yeast Saccharomyces cerevisiae have produced the largest, richest and most systematic phenotypic description of any organism. Such an achievement was enabled by the development of highly scalable phenotypic assays and construction of the yeast knock-out (YKO) collection, comprising ~5,000 isogenic strains each deleted for exactly one open reading frame. Systematic screening of the YKO collection led to ~500 publications describing ~14,500 phenotypes capturing nearly every aspect of yeast biology. Yet, integrative analyses of this rich data source have been virtually impossible due to the lack of a central repository and consistent meta-data annotations. Here, we describe the aggregation, harmonization and analysis of all published phenotypic screens of the YKO collection, which we refer to as the Yeast Phenome (www.yeastphenome.org). To demonstrate the power of data integration and illustrate how much it facilitates the generation of testable hypotheses, we present three discoveries uniquely enabled by Yeast Phenome. First, we use the variation in the number of phenotypes per gene to identify tryptophan homeostasis as a central point of vulnerability to a wide range of chemical compounds, including FDA-approved drugs. Second, using phenotypic profiles as a tool for predicting gene function, we identify and validate the role of YHR045W as a novel regulator of ergosterol biosynthesis and DNA damage response, and YGL117W as a new member of the aromatic amino acid biosynthesis pathway. Finally, we describe a surprising exponential relationship between phenotypic similarity and intergenic distance in both yeast and human genomes. This relationship, which stretches as far as 380 kb in yeast and 100 Mb in humans, suggests that gene positions are optimized for function to a much greater extent than appreciated previously. Overall, we show that Yeast Phenome enables systematic enquiries into the nature of gene-gene and gene-phenotype relationships and is an important new resource for systems biology.

systems biology↗

bioRxiv2020

How old are dragonflies and damselflies? Odonata (Insecta) transcriptomics resolve familial relationships

Dragonflies and damselflies, representing the insect order Odonata, are among the earliest flying insects with living (extant) representatives. However, unravelling details of their long evolutionary history, such as egg laying (oviposition) strategies, is impeded by unresolved phylogenetic relationships, an issue particularly prevalent in damselfly families and fossil lineages. Here we present the first transcriptome-based phylogenetic reconstruction of Odonata, analyzing 2,980 protein-coding genes in 105 species representing nearly all of the orders families (except Austropetaliidae and Neopetaliidae). All damselfly families and most dragonfly families are recovered as monophyletic groups. Our Molecular clock estimates suggest that crown-Zygoptera (damselflies) and -Anisoptera (dragonflies) both arose during the late Triassic. Several of the observed long inner branches in our topology are indicative of the extinction of once flourishing lineages. We also find that exophytic egg laying behaviour with a reduced ovipositor evolved in certain dragonflies during the late Jurassic / early Cretaceous. Lastly, we find that certain fossils have an unexpected deterring impact in divergence dating analysis.

evolutionary biology↗

bioRxiv2017

A Posteriori Evaluation Of Molecular Divergence Dates Using Empirical Estimates Of Time-Heterogeneous Fossilization Rates

The application of molecular clock concepts in phylogenetics permits estimating the divergence times of clades with an incomplete fossil record. However, the reliability of this approach is disputed, because the resulting estimates are often inconsistent with different sets of fossils and other parameters (clock models and prior settings) in the analyses. Here, we present the {lambda} statistic, a likelihood approach for a posteriori evaluating the reliability of estimated divergence times. The {lambda} statistic is based on empirically derived fossilization rates and evaluates the fit of estimated divergence times to the fossil record. We tested the performance of this measure with simulated data sets. Furthermore, we applied it to the estimated divergence times of (i) Clavigeritae beetles of the family Staphylinidae and (ii) all extant insect orders. The reanalyzed beetle data supports the originally published results, but shows that several fossil calibrations used do not increase the reliability of the divergence time estimates. Analyses of estimated inter-ordinal insect divergences indicate that uniform priors with soft bounds marginally outperform log-normal priors on node ages. Furthermore, a posteriori evaluation of the original published analysis indicates that several inter-ordinal divergence estimates might be too young. The {lambda} statistic allows the comparative evaluation of any clade divergence estimate derived from different calibration approaches. Consequently, the application of different algorithms, software tools, and calibration schemes can be empirically assessed.

paleontology↗