Reconstructing gene expression and knockout effect scores from DNA mutation (Mut2Ex): methodology and application to cancer prediction problems

Building prediction models for outcomes of clinical relevance when only a limited number of mutational features are available causes considerable challenges due to the sparseness and low-dimensionality of the data. In this article, we present a method to augment the predictive power of these features by leveraging multi-modal associative relationships between an individual's mutational profile and their corresponding gene expression or knockout effect profiles. We can thus reconstruct expression or effect scores for genes of interest from the available mutation features and then use this reconstructed representation directly to model and predict clinical outcomes. We show that our method produces significant improvements in predictive accuracy compared to models utilizing only the raw mutational data, and results in conclusions comparable to those obtained using real expression or effect profiles.Comment: 9 pages, 3 figure

New skin for the old RNA-Seq ceremony: the age of single-cell multi-omics

Abstract New methods for simultaneously quantifying protein and gene expression at the single-cell level have the power to identify cell types and to classify cell populations

Genome Analysis of a Novel Broad Host Range Proteobacteria Phage Isolated from a Bioreactor Treating Industrial Wastewater

Bacteriophages are viruses that infect bacteria, and consequently they have a major impact on the development of a microbial population. In this study, the genome of a novel broad host range bacteriophage, Aquamicrobium phage P14, isolated from a wastewater treatment plant, was analyzed. The Aquamicrobium phage P14 was found to infect members of different Proteobacteria classes (Alphaproteobacteria and Betaproteobacteria). This phage contains a 40,551 bp long genome and 60% of its genes had blastx hits. Furthermore, the bacteriophage was found to share more than 50% of its genes with several podoviruses and has the same gene order as other polyvalent bacteriophages. The results obtained in this study led to the conclusion that indeed general features of the genome of the Aquamicrobium phage P14 are shared with other broad host range bacteriophages, however further analysis of the genome is needed in order to identify the specific mechanisms which enable the bacteriophage to infect both Alphaproteobacteria and Betaproteobacteria

Molecular insights into bacteriophage evolution toward its host

Bacteriophages (phages), viruses that infect bacteria, are considered to be highly host-specific. To add to the knowledge about the evolution and development of bacteriophage speciation toward its host, we conducted a 21-day experiment with the broad host-range bacteriophage Aquamicrobium phage P14. We incubated the phage, which was previously isolated and enriched with the Alphaproteobacteria Aquamicrobium H14, with the Betaproteobacteria Alcaligenaceae H5. During the experiment, we observed an increase in the phage’s predation efficacy towards Alcaligenaceae H5. Furthermore, genome analysis and the comparison of the bacteriophage’s whole genome indicated that rather than being scattered evenly along the genome, mutations occur in specific regions. In total, 67% of the mutations with a frequency higher than 30% were located in genes that encode tail proteins, which are essential for host recognition and attachment. As control, we incubated the phage with the Alphaproteobacteria Aquamicrobium H8. In both experiments, most of the mutations appeared in the gene encoding the tail fiber protein. However, mutations in the gene encoding the tail tubular protein B were only observed when the phage was incubated with Alcaligenaceae H5. This highlights the phage’s tail as a key player in its adaptation to different hosts. We conclude that mutations in the phage’s genome were mainly located in tail-related regions. Further investigation is needed to fully characterize the adaptation mechanisms of the Aquamicrobium phage P14

A Generalist Protist Predator Enables Coexistence in Multitrophic Predator-Prey Systems Containing a Phage and the Bacterial Predator Bdellovibrio

Complex ecosystems harbor multiple predators and prey species whose direct and indirect interactions are under study. In particular, the combined effects of predator diversity and resource preference on prey removal are not known. To understand the effect of interspecies interactions, combinations of micro-predators—i.e., protists (generalists), predatory bacteria (semi-specialists), and phages (specialists)—and bacterial prey were tracked over a 72-h period in miniature membrane bioreactors. While specialist predators alone drove their preferred prey to extinction, the inclusion of a generalist resulted in uniform losses among prey species. Most importantly, presence of a generalist predator enabled coexistence of all predators and prey. As the generalist predator also negatively affected the other predators, we suggest that resource partitioning between predators and the constant availability of resources for bacterial growth due to protist predation stabilizes the system and keeps its diversity high. The appearance of resistant prey strains and subsequent evolution of specialist predators unable to infect the ancestral prey implies that multitrophic communities are able to persist and stabilize themselves. Interestingly, the appearance of BALOs and phages unable to infect their prey was only observed for the BALO or phage in the absence of additional predators or prey species indicating that competition between predators might influence coevolutionary dynamics