Biology subjects

Meyer, I. M.

Publications and source records attributed to Meyer, I. M..

4 recordsLinked to original sources

bioRxiv2021

Investigating the concept of accessibility for predicting novel RNA-RNA interactions

State-of-the-art methods for predicting novel trans RNA-RNA interactions use the so-called accessibility as key concept. It estimates whether a region in a given RNA sequence is accessible for forming trans interactions, using a thermodynamic model which quantifies its secondary structure features. RNA-RNA interactions are then predicted by finding the minimum free energy base-pairing between the two transcripts, taking into account the accessibility as energy penalty. We investigated the underlying assumptions of this approach using the two methods RNAO_SCPLOWPLEXC_SCPLOW and IO_SCPLOWNTAC_SCPLOWRNA on two datasets, containing sRNA-mRNA and snoRNA-rRNA interactions, respectively. We find that (1) known trans RNA-RNA interactions frequently overlap regions containing RNA structure features, (2) the estimated accessibility reflects sRNA structures fairly well, but often disagrees with structure annotations of longer transcripts, (3) the prediction performance of RNA-RNA interaction prediction methods is independent of the quality of the estimated accessibility profiles, and (4) one important overall effect of accessibility profiles is to prevent the thermodynamic model from predicting too long interactions. Based on our findings, we conclude that the accessibility concept to the minimum free energy approach to predicting novel RNA-RNA interactions has conceptual limitations and discuss potential ways of improving the field in the future.

bioinformatics↗

bioRxiv2021

CYCLeR - a novel tool for the full isoform assembly and quantification of circRNAs

Splicing is one key mechanism determining the state of any eukaryotic cell. Apart from linear splice variants, circular splice variants (circRNAs) can arise via non-canonical splicing involving a back-splice junction (BSJ). Most existing methods only identify circRNAs via the corresponding BSJ, but do not aim to estimate their full sequence identity or to identify different, alternatively spliced circular isoforms arising from the same BSJ. We here present CYCLO_SCPLOWEC_SCPLOWR, the first computational method for identifying the full sequence identify of new and alternatively spliced circRNAs and their abundances while simultaneously co-estimating the abundances of known linear splicing isoforms. We show that CYCLO_SCPLOWEC_SCPLOWR significantly out-performs existing methods in terms of sensitivity, precision and quantification of transcripts. When analysing D. melanogaster data, CYCLO_SCPLOWEC_SCPLOWR uncovers biological patterns of circRNA expression that other methods fail to observe.

bioinformatics↗

bioRxiv2019

BIQ: A method for searching circular RNAs in transcriptome databases by indexing backsplice junctions

Circular RNAs (circRNAs) are a class of RNA transcripts that originate from non-canonical splicing events and are characterized by a backsplice junction connecting the 3 splice site to an upstream 5 splice site. Here, we present the program BIQ for indexing and querying transcriptome sequencing datasets for backsplice junctions. BIQ can be used for instantaneously querying all indexed transcriptomes for occurrence and abundance of reads overlapping the backsplice junction of a particular circular RNA, which can help in the functional characterization of known and novel circular RNAs. BIQ is free software and available at https://github.com/pmenzel/biq.

bioinformatics↗

bioRxiv2018

The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant

A century ago, influenza A virus (IAV) infection caused the 1918 flu pandemic and killed an estimated 20-40 million people. Pandemic IAV outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular details of this species barrier are incompletely understood. We combined metabolic pulse labeling and quantitative shotgun proteomics to globally monitor protein synthesis upon infection of human cells with a human-and a bird-adapted IAV strain. While production of host proteins was remarkably similar, we observed striking differences in the kinetics of viral protein synthesis over the course of infection. Most importantly, the matrix protein M1 was inefficiently produced by the bird-adapted strain at later stages. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Experiments with reporter constructs and recombinant influenza viruses revealed that strain-specific M segment splicing is controlled by the 3 splice site and functionally important for permissive infection. Independent in silico evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, our data identifies M segment RNA splicing as a viral determinant of host range.

systems biology↗