Computational pan-genomics: status, promises and challenges

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains

Morphological, ecological, and molecular analyses separate Muraena augusti from Muraena helena as a valid species

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Tension band wiring for simple olecranon fractures: evaluation of surgical technique

Background: In some settings, specific techniques for open reduction and internal fixation are preferred based on the eminence of a surgeon or professional organization. An emphasis on technical aspects of surgery that are not proved superior and vary substantially from surgeon to surgeon can be confusing for trainees. This study applied a numerical grading of the technical aspects of tension band wire (TBW) fixation for olecranon fracture; assessed the interobserver agreement of each criterion; and measured the correlation of the technical grading and objective and subjective long-term outcomes. Materials and methods Forty observers were invited to rate the technical aspects of TBW fixation of the olecranon on 26 post-operative radiographs. The interobserver reliability of the rating was measured using the intra-class correlation coefficient. The correlation between the rating and motion, Mayo elbow performance index, and disabilities of the arm, shoulder and hand score was tested with the Spearman’s rank correlation test. Results: None of the figure-of-eight TBW constructs were considered perfect according to the numerical grading: the majority of observers found three deviations per fixation. The interobserver agreement was only fair for the total number of deviations and no correlation between the number of deviations and long-term objective and subjective outcome was found. Conclusions: A rating of the technical aspects of TBW for olecranon fractures was unreliable and did not correlate with subjective and objective outcomes. Emphasis on specific technical aspects of fixation might be confusing for trainees and could distract them from the principles of effective treatment. Level of evidence Level IV diagnostic study

Whole-genome sequence variation, population structure and demographic history of the Dutch population

Contains fulltext : 137213.pdf (publisher's version ) (Closed access)Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage ( approximately 13x) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies