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Szwed, A.

Publications and source records attributed to Szwed, A..

2 recordsLinked to original sources

Application of a new data management system to the study ofthe gut microbiome of children who are small for theirgestational age

Microbiome studies aim to answer the following questions: which organisms are in the sample and what is their impact on the patient or the environment? To answer these questions, investigators have to perform comparative analyses on their classified sequences based on the collected metadata, such as treatment, condition of the patient, or the environment. The integrity of sequences, classifications, and metadata is paramount for the success of such studies. Still, the area of data management for the preliminary study results appears to be neglected. Here, we present the development of a central data management system with an accessible web interface for the study of the gut microbiome in children who are small for their gestational age. We have called this system MetagenomicsDB. The web interface allows users, regardless of their bioinformatics expertise, to operate the system. The interface contains links to external resources in order to facilitate literature search, statistical analyses, and assessments of the potential pathogenicity of taxa. Preliminary study results are automatically quality-controlled and subsequently imported into a relational database. After exploration and optional filtering by the user, data are exported in a format directly suitable for follow-up analyses. Compared to a more conventional approach of storing the data in plain files, the automated quality control and database storage offered by MetagenomicsDB provides an enhanced quality assurance of the produced study results. This is especially true in a collaborative setting. Also, the automation of the data transfer from the format of the input data to the format needed for downstream analyses makes basic statistical and bioinformatic analyses accessible. The web interface not only allows us to perform our internal analyses, but will also facilitate transparent sharing of the complete study results at publication time with reviewers and the general public. We demonstrated the viability of this approach by making a subset of our preliminary study results already publicly accessible: https://www.bioinformatics.uni-muenster.de/tools/metagenomicsDB In the context of our study, our system provided more flexibility to conduct study- specific analyses and to integrate specific external resources than existing and necessarily more generic solutions. Our system is not yet ready to be widely applicable out-of-the-box for any microbiome study. However, we expect that due to the modular concept, the tests, and the extensive description of the underlying rationale, large parts of our implementation can be adapted for future projects in a fraction of the time needed to develop a new data management system from scratch. Thus, we report our endeavors in order to motivate the application of data management systems at the scale of single studies in microbiome research.

bioinformatics↗

3D images of Neuronal Adhesion Molecule Contactin-2 Reveal an Unanticipated Two-State Architecture

Contactins (CNTNs) are important cell adhesion molecules that mediate neuronal and axoglial contacts, and lesions in these molecules are linked to neuropsychiatric disorders. The extracellular domain of CNTNs contains six Ig domains and four FNIII domains. Crystal structures have shown that Ig1-Ig4 forms a horseshoe-shaped headpiece, in which the N-terminal domains might fold back on the C-terminal domains to form molecular super-U shaped architecture. The arrangement of these domains has been controversial, which may due to the structural dynamics and conformation heterogeneity of the protein. Here, we used a single-molecule 3D imaging method, individual-particle electron tomography (IPET), to study the extracellular domain of CNTN2 that forms monomers with a broad spectrum of conformations, and obtained 60 three-dimensional (3D) reconstructions. In addition to the known horseshoe-shaped headpiece, ~75% headpieces unexpectedly adopt an open (elongated) or a semi-open conformations contributed to our understanding about structural dynamics. The ectodomains formed curve but not double-back in any uniform way, with an averaged molecular dimension of ~255 [A]. The first-time demonstration of the dynamic nature and conformational preferences of the full-length CNTN2 ectodomain suggest that the headpiece exists in equilibrium in the closed or not-closed states. The important architecture may provide a structural platform for protein partners to influence this balance regulating the function of CNTN2. Encoding the ability of this neural adhesion molecule to form both homomers with itself, as well as recruit different protein partner to neuronal and axoglial contact points play the key role in mediating cell-cell interactions.

biochemistry↗