NcDNAlign: Plausible multiple alignments of non-protein-coding genomic sequences

Genome-wide multiple sequence alignments (MSAs) are a necessary prerequisite for an increasingly diverse collection of comparative genomic approaches. Here we present a versatile method that generates high-quality MSAs for non-protein-coding sequences. The NcDNAlign pipeline combines pairwise BLAST alignments to create initial MSAs, which are then locally improved and trimmed. The program is optimized for speed and hence is particulary well-suited to pilot studies. We demonstrate the practical use of NcDNAlign in three case studies: the search for ncRNAs in gammaproteobacteria and the analysis of conserved noncoding DNA in nematodes and teleost fish, in the latter case focusing on the fate of duplicated ultra-conserved regions. Compared to the currently widely used genome-wide alignment program TBA, our program results in a 20- to 30-fold reduction of CPU time necessary to generate gammaproteobacterial alignments. A showcase application of bacterial ncRNA prediction based on alignments of both algorithms results in similar sensitivity, false discovery rates, and up to 100 putatively novel ncRNA structures. Similar findings hold for our application of NcDNAlign to the identification of ultra-conserved regions in nematodes and teleosts. Both approaches yield conserved sequences of unknown function, result in novel evolutionary insights into conservation patterns among these genomes, and manifest the benefits of an efficient and reliable genome-wide alignment package. The software is available under the GNU Public License at http://www.bioinf.uni-leipzig.de/Software/NcDNAlign/

Respiratory infections in children and adolescents in Germany during the COVID-19 pandemic

Background: Before the COVID-19 pandemic, acute respiratory infections (ARIs) in children were mainly characterised by three pathogens: respiratory syncytial viruses (RSV), influenza viruses and rhinoviruses. The impact of the COVID-19 pandemic and the measures taken in Germany (especially until the end of 2021) on the incidence of ARI in children and adolescents aged 0 to 14 years and the pathogens causing them has not yet been comprehensively analysed. Methods: The evaluation is based on data from population-based, virological and hospital-based surveillance instruments up to the end of 2022. Results: After the onset of the COVID-19 pandemic in early 2020, ARI rates remained almost consistently below pre-pandemic levels until autumn 2021, with only rhinoviruses continuously continuing to cause ARI. Only when the Omicron variant became predominant in 2022, there were measurable COVID-19 rates at population level in children, although COVID-19 hospitalisation rates remained comparatively low. RSV and influenza waves were initially absent and then occurred ‘out of season’, but were more severe than usual. Conclusions: While the measures taken were effective in inhibiting the number of respiratory infections for almost 1.5 years, moderately frequent but rather mild COVID-19 cases occurred when measures were lifted. When Omicron emerged in 2022 COVID-19 became moderately frequent but led predominantly to mild illnesses. For RSV and influenza, the measures resulted in changes in their annual timing and intensity

Computational RNomics of Drosophilids

Recent experimental and computational studies have provided overwhelming evidence for a plethora of diverse transcripts that are unrelated to protein-coding genes. One subclass consists of those RNAs that require distinctive secondary structure motifs to exert their biological function and hence exhibit distinctive patterns of sequence conservation characteristic for positive selection on RNA secondary structure. The deep-sequencing of 12 drosophilid species coordinated by the NHGRI provides an ideal data set of comparative computational approaches to determine those genomic loci that code for evolutionarily conserved RNA motifs. This class of loci includes the majority of the known small ncRNAs as well as structured RNA motifs in mRNAs. We report here on a genome-wide survey using RNAz

Inferring Non-Coding RNA Families and Classes by Means of Genome-Scale Structure-Based Clustering

The RFAM database defines families of ncRNAs by means of sequence similarities that are sufficient to establish homology. In some cases, such as microRNAs and box H/ACA snoRNAs, functional commonalities define classes of RNAs that are characterized by structural similarities, and typically consist of multiple RNA families. Recent advances in high-throughput transcriptomics and comparative genomics have produced very large sets of putative noncoding RNAs and regulatory RNA signals. For many of them, evidence for stabilizing selection acting on their secondary structures has been derived, and at least approximate models of their structures have been computed. The overwhelming majority of these hypothetical RNAs cannot be assigned to established families or classes. We present here a structure-based clustering approach that is capable of extracting putative RNA classes from genome-wide surveys for structured RNAs. The LocARNA (local alignment of RNA) tool implements a novel variant of the Sankoff algorithm that is sufficiently fast to deal with several thousand candidate sequences. The method is also robust against false positive predictions, i.e., a contamination of the input data with unstructured or nonconserved sequences. We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments. Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis. Bioinformatics 21 (Supplement 2): i77–i78). In addition to recovering, e.g., tRNAs as a structure-based class, the method identifies several RNA families, including microRNA and snoRNA candidates, and suggests several novel classes of ncRNAs for which to date no representative has been experimentally characterized

ARE-Wochenbericht

Die Aktivität der akuten Atemwegserkrankungen (ARE-Raten) in der Bevölkerung (GrippeWeb) ist in der 25. KW 2022 im Vergleich zur Vorwoche stabil geblieben. Bei den Kindern (0 bis 14 Jahre) gab es einen Rückgang, bei den Erwachsenen (ab 15 Jahre) sind die Werte dagegen gestiegen oder stabil geblieben. Im ambulanten Bereich (Arbeitsgemeinschaft Influenza) wurden in der 25. KW bundesweit deutlich mehr Arztbesuche wegen ARE registriert als in der Vorwoche. Dabei sind die Werte in allen Altersgruppen gestiegen. Im NRZ für Influenzaviren wurden in der 25. KW 2022 in insgesamt 53 (62 %) der 85 eingesandten Sentinelproben respiratorische Viren identifiziert, darunter 17 (20 %) Proben mit SARS-CoV-2, 13 (15 %) mit Parainfluenzaviren (PIV), elf (13 %) mit Rhinoviren, sieben (8 %) mit Influenzaviren, vier (5 %) mit humanen Metapneumoviren (hMPV) und drei (4 %) mit humanen saisonalen Coronaviren (hCoV). Respiratorische Synzytialviren (RSV) wurden nicht nachgewiesen. Im Rahmen der ICD-10-Code basierten Krankenhaussurveillance (ICOSARI) ist die Zahl schwerer akuter respiratorischer Infektionen (SARI) in der 25. KW 2022 insgesamt leicht zurückgegangen

ARE-Wochenbericht

Die Aktivität der akuten Atemwegserkrankungen (ARE-Raten) in der Bevölkerung (GrippeWeb) ist in der 32. KW 2022 im Vergleich zur Vorwoche gestiegen. Die Werte liegen auf einem höheren Niveau als in den Vorjahren. Im ambulanten Bereich (Arbeitsgemeinschaft Influenza) wurden in der 32. KW bundesweit weniger Arztbesuche wegen ARE registriert als in der Vorwoche. Die Zahl der Arztbesuche liegt weiterhin deutlich über dem Niveau der Vorjahre (seit 2006) um diese Zeit. Im NRZ für Influenzaviren wurden in der 32. KW 2022 in insgesamt 27 (51 %) der 53 eingesandten Sentinelproben respiratorische Viren identifiziert, darunter zwölf (23 %) mit SARS-CoV-2 Proben, jeweils sechs (11 %) mit Parainfluenza- (PIV) bzw. Rhinoviren, zwei (4 %) mit Influenzaviren und eine Probe (2 %) mit humanen Metapneumoviren. Es wurden in keiner Probe Respiratorische Synzytial- oder humane saisonale Coronaviren detektiert. In den Sommerwochen werden aufgrund der Ferien- und Urlaubszeit weniger Proben eingeschickt. Im Rahmen der ICD-10-Code basierten Krankenhaussurveillance (ICOSARI) ist die Zahl schwerer akuter respiratorischer Infektionen (SARI) in der 32. KW 2022 insgesamt gesunken. In den Altersgruppen unter 80 Jahren liegen die SARI-Fallzahlen auf einem während der Sommermonate üblichen Niveau, bei den ab 80-Jährigen werden jedoch weiterhin noch etwas höhere Fallzahlen beobachtet als in den Vorsaisons. Die im Vergleich mit den Vorjahren aktuell noch deutlich höhere ARE-Aktivität ist auf die Ko-Zirkulation verschiedener Atemwegserreger zurückzuführen. Hierbei werden hauptsächlich SARS-CoV-2 bei Erwachsenen sowie Parainfluenza- und Rhinoviren bei Kindern nachgewiesen. In den letzten Wochen wurde sporadisch RSV in Sentinelproben identifiziert, in der 31. KW und 32. KW 2022 gab es jedoch keine RSV-Nachweise