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Background: The exploration of the microbial world has been greatly advanced by the reconstruction of genomes from metagenomic sequence data. However, the rapidly increasing number of metagenome-assembled genomes has also resulted in a wide variation in data quality. It is therefore essential to quantify the achieved completeness and possible contamination of a reconstructed genome before it is used in subsequent analyses. The classical approach for the estimation of quality indices solely relies on a relatively small number of universal single-copy genes. Recent tools try to extend the genomic coverage of estimates for an increased accuracy., Results: We developed CoCoPyE, a fast tool based on a novel 2-stage feature extraction and transformation scheme. First, it identifies genomic markers and then refines the marker-based estimates with a machine learning approach. In our simulation studies, CoCoPyE showed a more accurate prediction of quality indices than the existing tools. While the CoCoPyE web server offers an easy way to try out the tool, the freely available Python implementation enables integration into existing genome reconstruction pipelines., Conclusions: CoCoPyE provides a new approach to assess the quality of genome data. It complements and improves existing tools and may help researchers to better distinguish between low-quality draft and high-quality genome assemblies in metagenome sequencing projects., (© The Author(s) 2024. Published by Oxford University Press GigaScience.)

Background: A major challenge in neurodegenerative diseases concerns identifying biological disease signatures that track with disease progression or respond to an intervention. Several clinical trials in Huntington disease (HD), an inherited, progressive neurodegenerative disease, are currently ongoing. Therefore, we examine whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in HD patients., Results: We generate large, high-quality human datasets from skeletal muscle, skin and adipose tissue to probe molecular changes in human premanifest and early manifest HD patients-those most likely involved in clinical trials. The analysis of the transcriptomics and proteomics data shows robust, stage-dependent dysregulation. Gene ontology analysis confirms the involvement of inflammation and energy metabolism in peripheral HD pathogenesis. Furthermore, we observe changes in the homeostasis of extracellular vesicles, where we find consistent changes of genes and proteins involved in this process. In-depth single nucleotide polymorphism data across the HTT gene are derived from the generated primary cell lines., Conclusions: Our 'omics data document the involvement of inflammation, energy metabolism, and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials. The generated data, complemented by the primary cell lines established from peripheral tissues, and a large panel of iPSC lines that can serve as human models of HD are a valuable and unique resource to advance the current understanding of molecular mechanisms driving HD pathogenesis., (© 2022. The Author(s).)

Most methods for phylogenetic tree reconstruction are based on sequence alignments; they infer phylogenies from substitutions that may have occurred at the aligned sequence positions. Gaps in alignments are usually not employed as phylogenetic signal. In this paper, we explore an alignment-free approach that uses insertions and deletions (indels) as an additional source of information for phylogeny inference. For a set of four or more input sequences, we generate so-called quartet blocks of four putative homologous segments each. For pairs of such quartet blocks involving the same four sequences, we compare the distances between the two blocks in these sequences, to obtain hints about indels that may have happened between the blocks since the respective four sequences have evolved from their last common ancestor. A prototype implementation that we call Gap-SpaM is presented to infer phylogenetic trees from these data, using a quartet-tree approach or, alternatively, under the maximum-parsimony paradigm. This approach should not be regarded as an alternative to established methods, but rather as a complementary source of phylogenetic information. Interestingly, however, our software is able to produce phylogenetic trees from putative indels alone that are comparable to trees obtained with existing alignment-free methods., Competing Interests: The authors have declared that no competing interests exist.

There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals. Mitochondrial morphology was determined using electron microscopy, and transcript and protein levels of factors that play a key role in fission and fusion, including DRP1, mitofusin 1 and 2, mitofilin and OPA1, and cytochrome c and caspase 3 were assessed by RT-qPCR and immunoblotting. OPA1 oligomerisation was evaluated using blue native gels. In striatum and cortex of R6/2 mice, mitochondrial cristae morphology was abnormal. Mitofilin and the overall levels of the fission and fusion factors were unaffected; however, OPA1 oligomerisation was abnormal in striatum and cortex of R6/2 mice. Mitochondrial and cytoplasmic cytochrome c levels were similar in R6/2 and wild-type mice with no significant increase of activated caspase 3. Our results indicate that the integrity of the mitochondrial cristae is compromised in striatum and cortex of the R6/2 mice and that this is most likely caused by impaired OPA1 oligomerisation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In Huntington's disease (HD) the striatum and cortex seem particularly vulnerable. Mitochondrial dysfunction can also cause neurodegeneration with prominent striatal involvement very similar to HD. We first examined if mitochondrial biogenesis, mitochondrial DNA (mtDNA) transcription, and the implications for mitochondrial respiratory chain (MRC) assembly and function differ between the striatum and cortex compared with the whole brain average in the healthy mouse brain. We then examined the effects of the mutant huntingtin transgene in end-stage R6/2 mice. In wild-type mice, mitochondrial mass (citrate synthase levels, mtDNA copy number) was higher in the striatum than in the cortex or whole brain average. PGC-1α and TFAM mRNA levels were also higher in the striatum than the whole brain average and cortex. mRNA reserve for MRC Complex proteins was higher in the striatum and cortex. In addition, in the cortex a greater part of mitochondrial mass was dedicated to the generation of ATP by oxidative phosphorylation than in the striatum or on average in the brain. In the HD transgenic striatum there was selective mtDNA depletion without evidence that this translated to abnormalities of steady-state MRC function. Our data indicate that in mice the striatum differs from the cortex, or whole brain average, in potentially important aspects of mitochondrial biology. This may contribute to the increased vulnerability of the striatum to insults such as the HD mutation, causing selective striatal mtDNA depletion in end-stage R6/2 mice., (Copyright © 2015 Elsevier Inc. All rights reserved.)