Next Generation Complex Genome Assembly

Whole genome assembly boosts the discovery of genes and pathways involved in the key metabolites produced in medicinal plants. Many medicinal plants possess large, polyploid and/or heterozygote genomes, thus denovo assembly of these genomes poses a significant challenge both algorithmically and economically. DeNovoMAGIC-2 assembler has successfully reconstructed some of the largest most repetitive, polyploid and heterozygote plant genomes. Using only high coverage of short Illumina reads, DeNovoMAGIC-2 has assembled over 90 % of the genome sequence of the 16 Gb, hexaploid wheat and the 1 Gb, tetraploid and heterozygote mango genome, with N50 of ~7 Mb and ~1 Mb respectively. Assemblies were completed in 14 and 2 days using 1 Tb and 0.512 Tb RAM computers, respectively. BUSCO analysis revealed full intact gene content for over 90 % of the genome, with clear phasing of allelic and paralog genes. Similar employment of DeNovoMAGIC-2 is expected to reconstruct the genome sequences of many medicinal plants, boosting our basic understanding of metabolite production and accumulation, towards industrializing medicine production from plants

Examining the synergistic effects of a cognitive control video game and a home-based, self-administered non-invasive brain stimulation on alleviating depression : the DiSCoVeR trial protocol

Funding Information: Open Access funding enabled and organized by Projekt DEAL. The DisCoVeR project is funded by ERA NET NEURON. The NEURON ‘Network of European Funding for Neuroscience Research is established under the organization of the ERA-NET ‘European Research Area Networks’ of the European Commission. National funding agencies are the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung [BMBF]) for LMU Munich, the Ministry of Health (MOH) for HUJI and Hadassah, the Swiss National Science Foundation (SNSF) for UNIGE and EPFL and the State Education and Development Agency (VIAA) of Latvia for RSU. Funding Information: This project was funded by the European Research Area Network (ERA-NET) NEURON 2018 Mental Disorders program. Publisher Copyright: © 2022, The Author(s).Enhanced behavioral interventions are gaining increasing interest as innovative treatment strategies for major depressive disorder (MDD). In this study protocol, we propose to examine the synergistic effects of a self-administered home-treatment, encompassing transcranial direct current stimulation (tDCS) along with a video game based training of attentional control. The study is designed as a two-arm, double-blind, randomized and placebo-controlled multi-center trial (ClinicalTrials.gov: NCT04953208). At three study sites (Israel, Latvia, and Germany), 114 patients with a primary diagnosis of MDD undergo 6 weeks of intervention (30 × 30 min sessions). Patients assigned to the intervention group receive active tDCS (anode F3 and cathode F4; 2 mA intensity) and an action-like video game, while those assigned to the control group receive sham tDCS along with a control video game. An electrode-positioning algorithm is used to standardize tDCS electrode positioning. Participants perform their designated treatment at the clinical center (sessions 1-5) and continue treatment at home under remote supervision (sessions 6-30). The endpoints are feasibility (primary) and safety, treatment efficacy (secondary, i.e., change of Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week six from baseline, clinical response and remission, measures of social, occupational, and psychological functioning, quality of life, and cognitive control (tertiary). Demonstrating the feasibility, safety, and efficacy of this novel combined intervention could expand the range of available treatments for MDD to neuromodulation enhanced interventions providing cost-effective, easily accessible, and low-risk treatment options.ClinicalTrials.gov: NCT04953208.publishersversionPeer reviewe

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Partial exposure in large games

In this work we introduce the notion of partial exposure, in which the players of a simultaneous-move Bayesian game are exposed to the realized types and chosen actions of a subset of the other players. We show that in any large simultaneous-move game, each player has very little regret even after being partially exposed to other players. If players are given the opportunity to be exposed to others at the expense of a small decrease in utility, players will decline this opportunity, and the original Nash equilibria of the game will survive.Noncooperative games Large games Nash equilibrium Ex post Nash