Bucket Fuser: Statistical Signal Extraction for 1D 1H NMR Metabolomic Data

Untargeted metabolomics is a promising tool for identifying novel disease biomarkers and unraveling underlying pathomechanisms. Nuclear magnetic resonance (NMR) spectroscopy is particularly suited for large-scale untargeted metabolomics studies due to its high reproducibility and cost effectiveness. Here, one-dimensional (1D) 1H NMR experiments offer good sensitivity at reasonable measurement times. Their subsequent data analysis requires sophisticated data preprocessing steps, including the extraction of NMR features corresponding to specific metabolites. We developed a novel 1D NMR feature extraction procedure, called Bucket Fuser (BF), which is based on a regularized regression framework with fused group LASSO terms. The performance of the BF procedure was demonstrated using three independent NMR datasets and was benchmarked against existing state-of-the-art NMR feature extraction methods. BF dynamically constructs NMR metabolite features, the widths of which can be adjusted via a regularization parameter. BF consistently improved metabolite signal extraction, as demonstrated by our correlation analyses with absolutely quantified metabolites. It also yielded a higher proportion of statistically significant metabolite features in our differential metabolite analyses. The BF algorithm is computationally efficient and it can deal with small sample sizes. In summary, the Bucket Fuser algorithm, which is available as a supplementary python code, facilitates the fast and dynamic extraction of 1D NMR signals for the improved detection of metabolic biomarker

The Genome and Methylome of a Beetle with Complex Social Behavior,Nicrophorus vespilloides(Coleoptera: Silphidae)

Testing for conserved and novelmechanisms underlying phenotypic evolution requires a diversity of genomes available for comparisonspanning multiple independent lineages. For example, complex social behavior in insects has been investigated primarily witheusocial lineages, nearly all of which are Hymenoptera. If conserved genomic influences on sociality do exist, we need data from awider range of taxa that also vary in their levels of sociality. Here,we present the assembled and annotated genome of the subsocialbeetle Nicrophorus vespilloides, a species long used to investigate evolutionary questions of complex social behavior. We used thisgenome to address two questions. First, do aspects of life history, such as using a carcass to breed, predict overlap in gene modelsmore strongly than phylogeny? We found that the overlap in gene models was similar between N. vespilloides and all other insectgroups regardless of life history. Second, like other insects with highly developed social behavior but unlike other beetles, doesN. vespilloides have DNA methylation?We found strong evidence for an active DNA methylation system. The distribution of methylationwassimilar to other insects with exons having themostmethylatedCpGs. Methylation status appears highly conserved; 85%of themethylated genes in N. vespilloides are alsomethylated in the hymentopteran Nasonia vitripennis. The addition of this genomeadds a coleopteran resource to answer questions about the evolution and mechanistic basis of sociality and to address questionsabout the potential role of methylation in social behavior

TAp73 is a central transcriptional regulator of airway multiciliogenesis.

Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation

Enhanced genome assembly and a new official gene set for Tribolium castaneum

Background. The red flour beetle Tribolium castaneum has emerged as an important model organism for the study of gene function in development and physiology, for ecological and evolutionary genomics, for pest control and a plethora of other topics. RNA interference (RNAi), transgenesis and genome editing are well established and the resources for genome-wide RNAi screening have become available in this model. All these techniques depend on a high quality genome assembly and precise gene models. However, the first version of the genome assembly was generated by Sanger sequencing, and with a small set of RNA sequence data limiting annotation quality. Results. Here, we present an improved genome assembly (Tcas5.2) and an enhanced genome annotation resulting in a new official gene set (OGS3) for Tribolium castaneum, which significantly increase the quality of the genomic resources. By adding large-distance jumping library DNA sequencing to join scaffolds and fill small gaps, the gaps in the genome assembly were reduced and the N50 increased to 4753kbp. The precision of the gene models was enhanced by the use of a large body of RNA-Seq reads of different life history stages and tissue types, leading to the discovery of 1452 novel gene sequences. We also added new features such as alternative splicing, well defined UTRs and microRNA target predictions. For quality control, 399 gene models were evaluated by manual inspection. The current gene set was submitted to Genbank and accepted as a RefSeq genome by NCBI. Conclusions. The new genome assembly (Tcas5.2) and the official gene set (OGS3) provide enhanced genomic resources for genetic work in Tribolium castaneum. The much improved information on transcription start sites supports transgenic and gene editing approaches. Further, novel types of information such as splice variants and microRNA target genes open additional possibilities for analysis

The iBeetle large-scale RNAi screen reveals gene functions for insect development and physiology

Genetic screens are powerful tools to identify the genes required for a given biological process. However, for technical reasons, comprehensive screens have been restricted to very few model organisms. Therefore, although deep sequencing is revealing the genes of ever more insect species, the functional studies predominantly focus on candidate genes previously identified in Drosophila, which is biasing research towards conserved gene functions. RNAi screens in other organisms promise to reduce this bias. Here we present the results of the iBeetle screen, a large-scale, unbiased RNAi screen in the red flour beetle, Tribolium castaneum, which identifies gene functions in embryonic and postembryonic development, physiology and cell biology. The utility of Tribolium as a screening platform is demonstrated by the identification of genes involved in insect epithelial adhesion. This work transcends the restrictions of the candidate gene approach and opens fields of research not accessible in Drosophila

Foresight i proces generowania scenariuszy w Instytucie Fraunhofera ISI

The Fraunhofer Institute for Systems and Innovation Research ISI analyses the origins and impacts of innovations and research, the short- and long-term developments of innovation processes, and the impacts of new technologies and services on society. Apart from clients from industry, academia and politics, the Fraunhofer ISI supports futures dialogues and the strategy process within the Fraunhofer-Society itself. For this purpose, scientifically based analysis, evaluation, as well as foresight methods are applied and developed. The term “foresight” refers to a structured debate about complex futures that is based on a systematic approach using various methods of future research [5, 15, 16]. One of them is the scenario method that provides a systematic process of creating alternative pictures of the future integrating quantitative and qualitative data. The scenario method concerns the interaction with the relevant actors. The focus is on active preparation for the long-term future by inspiring future thinking and supporting action towards shaping the future. For this purpose, new approaches are constantly being developed or known ones are further advanced. A system perspective is always at the heart of the scenario process design. Hence, a look into the future needs to be broad and comprehensive, including multiple perspectives. In addition, the scenario method is open to different pathways into the future and to discussing alternative developments. For decisions to be taken today, a future has to be selected, to prepare for it, or to make it real. One option may also be a business-as-usual scenario for the future. It is important to clarify which future is being analysed: a possible future (What can happen?), a probable future (Which options do we have?), a desirable future or a vision (Where do we want to go?).W artykule przedstawiono wady i zalety generowania scenariuszy z wykorzystaniem warsztatów. Przeanalizowano dwa alternatywne podejścia ukierunkowane na zminimalizowanie wskazanych wad. Ponadto zaprezentowano typowe elementy procesu tworzenia scenariuszy w Instytucie Fraunhofera ISI w Niemczech