NanoDJ A Dockerized Jupyter Notebook for Interactive Oxford Nanopore MinION Sequence Manipulation and Genome Assembly, bioRxiv, 2019-03-28
AbstractBackgroundThe Oxford Nanopore Technologies (ONT) MinION portable sequencer makes it possible to use cutting-edge genomic technologies in the field and the academic classroom.ResultsWe present NanoDJ, a Jupyter notebook integration of tools for simplified manipulation and assembly of DNA sequences produced by ONT devices. It integrates basecalling, read trimming and quality control, simulation and plotting routines with a variety of widely used aligners and assemblers, including procedures for hybrid assembly.ConclusionsWith the use of Jupyter-facilitated access to self-explanatory contents of applications and the interactive visualization of results, as well as by its distribution into a Docker software container, NanoDJ is aimed to simplify and make more reproducible ONT DNA sequence analysis. The NanoDJ package code, documentation and installation instructions are freely available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsgithub.comgenomicsITERNanoDJ>httpsgithub.comgenomicsITERNanoDJ<jatsext-link>.
biorxiv bioinformatics 0-100-users 2019A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells, bioRxiv, 2019-03-25
AbstractResearch in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situ activation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation.
biorxiv immunology 0-100-users 2019Bacterial biodiversity drives the evolution of CRISPR-based phage resistance in Pseudomonas aeruginosa, bioRxiv, 2019-03-25
Approximately half of all bacterial species encode CRISPR-Cas adaptive immune systems1, which provide immunological memory by inserting short DNA sequences from phage and other parasitic DNA elements into CRISPR loci on the host genome2. Whereas CRISPR loci evolve rapidly in natural environments3, bacterial species typically evolve phage resistance by the mutation or loss of phage receptors under laboratory conditions4,5. Here, we report how this discrepancy may in part be explained by differences in the biotic complexity of in vitro and natural environments6,7. Specifically, using the opportunistic pathogen Pseudomonas aeruginosa and its phage DMS3vir, we show that coexistence with other human pathogens amplifies the fitness trade-offs associated with phage receptor mutation, and therefore tips the balance in favour of CRISPR-based resistance evolution. We also demonstrate that this has important knock-on effects for P. aeruginosa virulence, which became attenuated only if the bacteria evolved surface-based resistance. Our data reveal that the biotic complexity of microbial communities in natural environments is an important driver of the evolution of CRISPR-Cas adaptive immunity, with key implications for bacterial fitness and virulence.
biorxiv evolutionary-biology 0-100-users 2019Modulation of visual cortex by hippocampal signals, bioRxiv, 2019-03-25
Neurons in primary visual cortex (V1) are influenced by the animal’s position in the environment and encode positions that correlate with those encoded by hippocampus (CA1). Might V1’s encoding of spatial positions be inherited from hippocampal regions? If so, it should depend on non-visual factors that affect the encoding of position in hippocampus, such as the physical distance traveled and the phase of theta oscillations. We recorded V1 and CA1 neurons while mice ran through a virtual corridor and confirmed these predictions. Spatial representations in V1 and CA1 were correlated even in the absence of visual cues. Moreover, similar to CA1 place cells, the spatial responses of V1 neurons were influenced by the physical distance traveled and the phase of hippocampal theta oscillations. These results reveal a modulation of cortical sensory processing by non-sensory estimates of position that might originate in hippocampal regions.
biorxiv neuroscience 0-100-users 2019Bipartite anchoring of SCREAM enforces stomatal initiation by coupling MAP Kinases to SPEECHLESS, bioRxiv, 2019-03-24
AbstractCell-fate in eukaryotes is regulated by MAP Kinases (MAPKs) that translate external cues to cellular responses. In plants, two MAPKs, MPK36, regulate diverse processes of development, environmental response, and immunity. Yet, the mechanism bridging these shared signaling components with a specific target remains unresolved. Focusing on the development of stomata, epidermal valves for gas exchange and transpiration, we report here that the bHLH protein SCREAM functions as a scaffold by recruiting MPK36 to downregulate SPEECHLESS, a transcription factor initiating stomatal cell lineages. SCREAM directly binds with MPK36 through an evolutionarily-conserved yet unconventional bipartite motif. Mutations in this motif abrogate association, phosphorylation and degradation of SCREAM, unmask hidden non-redundancies between MPK3 and MPK6, and result in uncontrolled stomatal differentiation. Structural analyses of MPK6 at the 2.75Å resolution unraveled bipartite binding of SCREAM with MPK6, that is distinct from an upstream MAPKK. Our findings elucidate, at the atomic resolution, the mechanism directly linking extrinsic signals to transcriptional reprogramming during the establishment of stomatal cell-fate, and highlight a unique substrate-binding mode adopted by plant MAPKs.
biorxiv plant-biology 0-100-users 2019Spatial structure governs the mode of tumour evolution, bioRxiv, 2019-03-24
AbstractCharacterizing the mode – the way, manner, or pattern – of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. DNA sequencing studies have inferred various modes, including branching, punctuated and neutral evolution, but it is unclear why a particular pattern predominates in any given tumour.1, 2 Here we propose that differences in tumour architecture alone can explain the variety of observed patterns. We examine this hypothesis using spatially explicit population genetic models and demonstrate that, within biologically relevant parameter ranges, human tumours are expected to exhibit four distinct onco-evolutionary modes (oncoevotypes) rapid clonal expansion (predicted in leukaemia); progressive diversification (in colorectal adenomas and early-stage colorectal carcinomas); branching evolution (in invasive glandular tumours); and effectively almost neutral evolution (in certain non-glandular and poorly differentiated solid tumours). We thus provide a simple, mechanistic explanation for a wide range of empirical observations. Oncoevotypes are governed by the mode of cell dispersal and the range of cell-cell interaction, which we show are essential factors in accurately characterizing, forecasting and controlling tumour evolution.
biorxiv cancer-biology 0-100-users 2019