The mOTUs online database provides web-accessible genomic context to taxonomic profiling of microbial communities.

Determining the taxonomic composition (taxonomic profiling) is a fundamental task in studying environmental and host-associated microbial communities. However, genome-resolved microbial diversity on Earth remains undersampled, and accessing the genomic context of taxa detected during taxonomic profiling remains a challenging task. Here, we present the mOTUs online database (mOTUs-db), which is consistent with and interfaces with the mOTUs taxonomic profiling tool.

In silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications.

Alternative splicing is crucial for cancer progression and can be targeted pharmacologically, yet identifying driver exons genome-wide remains challenging. We propose identifying such exons by associating statistically gene-level cancer dependencies from knockdown viability screens with splicing profiles and gene expression. Our models predict the effects of splicing perturbations on cell proliferation from transcriptomic data, enabling in silico RNA screening and prioritizing targets for splicing-based therapies.

Disentangling the splicing factor programs underlying complex molecular phenotypes.

The regulation of exon inclusion through alternative splicing tunes the cell's behavior by increasing the functional diversity of the transcriptome and the proteome. Splicing factors work in concert to generate gene isoform pools that contribute to cell phenotypes yet their activity is controlled by multiple regulatory and signaling layers. This hinders identification of functional, phenotype-specific splicing factors using traditional single-omic measurements, such as their mutational state or expression.

robustica: customizable robust independent component analysis.

Background: Independent Component Analysis (ICA) allows the dissection of omic datasets into modules that help to interpret global molecular signatures. The inherent randomness of this algorithm can be overcome by clustering many iterations of ICA together to obtain robust components. Existing algorithms for robust ICA are dependent on the choice of clustering method and on computing a potentially biased and large Pearson distance matrix.

SURE editing: combining oligo-recombineering and programmable insertion/deletion of selection markers to efficiently edit the Mycoplasma pneumoniae genome.

The development of advanced genetic tools is boosting microbial engineering which can potentially tackle wide-ranging challenges currently faced by our society. Here we present SURE editing, a multi-recombinase engineering rationale combining oligonucleotide recombineering with the selective capacity of antibiotic resistance via transient insertion of selector plasmids. We test this method in Mycoplasma pneumoniae, a bacterium with a very inefficient native recombination machinery.

Specialization of the photoreceptor transcriptome by -dependent microexons is required for outer segment maintenance and vision.

Retinal photoreceptors have a distinct transcriptomic profile compared to other neuronal subtypes, likely reflecting their unique cellular morphology and function in the detection of light stimuli by way of the ciliary outer segment. We discovered a layer of this molecular specialization by revealing that the vertebrate retina expresses the largest number of tissue-enriched microexons of all tissue types. A subset of these microexons is included exclusively in photoreceptor transcripts, particularly in genes involved in cilia biogenesis and vesicle-mediated transport.

A genetic toolkit and gene switches to limit Mycoplasma growth for biosafety applications.

Mycoplasmas have exceptionally streamlined genomes and are strongly adapted to their many hosts, which provide them with essential nutrients. Owing to their relative genomic simplicity, Mycoplasmas have been used to develop chassis for biotechnological applications. However, the dearth of robust and precise toolkits for genomic manipulation and tight regulation has hindered any substantial advance.

LoxTnSeq: random transposon insertions combined with cre/lox recombination and counterselection to generate large random genome reductions.

The removal of unwanted genetic material is a key aspect in many synthetic biology efforts and often requires preliminary knowledge of which genomic regions are dispensable. Typically, these efforts are guided by transposon mutagenesis studies, coupled to deepsequencing (TnSeq) to identify insertion points and gene essentiality. However, epistatic interactions can cause unforeseen changes in essentiality after the deletion of a gene, leading to the redundancy of these essentiality maps.

FASTQINS and ANUBIS: two bioinformatic tools to explore facts and artifacts in transposon sequencing and essentiality studies.

Transposon sequencing is commonly applied for identifying the minimal set of genes required for cellular life; a major challenge in fields such as evolutionary or synthetic biology. However, the scientific community has no standards at the level of processing, treatment, curation and analysis of this kind data. In addition, we lack knowledge about artifactual signals and the requirements a dataset has to satisfy to allow accurate prediction.

Inferring Active Metabolic Pathways from Proteomics and Essentiality Data.

Here, we propose an approach to identify active metabolic pathways by integrating gene essentiality analysis and protein abundance. We use two bacterial species (Mycoplasma pneumoniae and Mycoplasma agalactiae) that share a high gene content similarity yet show significant metabolic differences. First, we build detailed metabolic maps of their carbon metabolism, the most striking difference being the absence of two key enzymes for glucose metabolism in M.

The role of clonal communication and heterogeneity in breast cancer.

Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones.

SynMyco transposon: engineering transposon vectors for efficient transformation of minimal genomes.

Mycoplasmas are important model organisms for Systems and Synthetic Biology, and are pathogenic to a wide variety of species. Despite their relevance, many of the tools established for genome editing in other microorganisms are not available for Mycoplasmas. The Tn4001 transposon is the reference tool to work with these bacteria, but the transformation efficiencies (TEs) reported for the different species vary substantially.

Alternative transcriptional regulation in genome-reduced bacteria.

Transcription is a core process of bacterial physiology, and as such it must be tightly controlled, so that bacterial cells maintain steady levels of each RNA molecule in homeostasis and modify them in response to perturbations. The major regulators of transcription in bacteria (and in eukaryotes) are transcription factors. However, in genome-reduced bacteria, the limited number of these proteins is insufficient to explain the variety of responses shown upon changes in their environment.

Engineering bacteria to form a biofilm and induce clumping in Caenorhabditis elegans.

Bacteria are needed for a vast range of biotechnological processes, which they carry out either as pure cultures or in association with other bacteria and/or fungi. The potential of bacteria as biofactories is hampered, though, by their limited mobility in solid or semisolid media such as agricultural or domestic waste. This work represents an attempt toward overcoming this limitation by associating bacterial biotechnological properties with the transport ability of the nematode Caenorhabditis elegans.