Simm, Dominic Alexander

[["dc.bibliographiccitation.artnumber","959"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Molecular systems biology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hatje, Klas"],["dc.contributor.author","Rahman, Raza-Ur"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Simm, Dominic"],["dc.contributor.author","Hammesfahr, Björn"],["dc.contributor.author","Bansal, Vikas"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Mickael, Michel Edwar"],["dc.contributor.author","Sun, Ting"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Kollmar, Martin"],["dc.date.accessioned","2019-07-30T10:25:25Z"],["dc.date.available","2019-07-30T10:25:25Z"],["dc.date.issued","2017"],["dc.description.abstract","Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression might predict human disease pathology."],["dc.identifier.doi","10.15252/msb.20177728"],["dc.identifier.pmid","29242366"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62194"],["dc.language.iso","en"],["dc.relation.eissn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.title","The landscape of human mutually exclusive splicing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Simm, Dominic"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Waack, Stephan"],["dc.contributor.author","Kollmar, Martin"],["dc.date.accessioned","2022-07-01T07:34:51Z"],["dc.date.available","2022-07-01T07:34:51Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Heterologous protein expression is an important method for analysing cellular functions of proteins, in genetic circuit engineering and in overexpressing proteins for biopharmaceutical applications and structural biology research. The degeneracy of the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, plays an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the influence of a profiled codon usage adaptation approach on protein expression levels in the eukaryotic model organism Saccharomyces cerevisiae . We selected green fluorescent protein (GFP) and human α-synuclein (αSyn) as representatives for stable and intrinsically disordered proteins and representing a benchmark and a challenging test case. A new approach was implemented to design typical genes resembling the codon usage of any subset of endogenous genes. Using this approach, synthetic genes for GFP and αSyn were generated, heterologously expressed and evaluated in yeast. We demonstrate that GFP is expressed at high levels, and that the toxic αSyn can be adapted to endogenous, low-level expression. The new software is publicly available as a web-application for performing host-specific protein adaptations to a set of the most commonly used model organisms ( https://odysseus.motorprotein.de )."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Georg-August-Universität Göttingen http://dx.doi.org/10.13039/501100003385"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-022-13089-1"],["dc.identifier.pii","13089"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112027"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2045-2322"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Design of typical genes for heterologous gene expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Simm, Dominic"],["dc.contributor.author","Hatje, Klas"],["dc.contributor.author","Waack, Stephan"],["dc.contributor.author","Kollmar, Martin"],["dc.date.accessioned","2019-07-30T10:11:31Z"],["dc.date.available","2019-07-30T10:11:31Z"],["dc.date.issued","2019"],["dc.description.abstract","Coiled-coil regions were among the first protein motifs described structurally and theoretically. The beauty and simplicity of the motif gives hope to detecting coiled-coil regions with reasonable accuracy and precision in any protein sequence. Here, we re-evaluated the most commonly used coiled-coil prediction tools with respect to the most comprehensive reference data set available, the entire Protein Data Base (PDB), down to each amino acid and its secondary structure. Apart from the thirtyfold difference in number of predicted coiled-coils the tools strongly vary in their predictions, across structures and within structures. The evaluation of the false discovery rate and Matthews correlation coefficient, a widely used performance metric for imbalanced data sets, suggests that the tested tools have only limited applicability for large data sets. Coiled-coil predictions strongly impact the functional characterization of proteins, are used for functional genome annotation, and should therefore be supported and validated by additional information."],["dc.identifier.doi","10.1101/675025"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62191"],["dc.language.iso","en"],["dc.title","Protein function prediction in genomes: Critical assessment of coiled-coil predictions based on protein structure data"],["dc.type","preprint"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]