Ewan Birney * E-mail: birney@ebi.ac.uk Affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom ...ORCID http://orcid.org/0000-0001-8314-8497Citation: Birney E (2016) The Mighty Fruit Fly Moves into Outbred Genetics. Ewan Birney is a paid consultant to both Oxford Nanopore and GSK companies, and a non-executive director of Genomics England Ltd. January 2016's issue of PLOS Genetics has an outbred genetics study in body size traits 1, perhaps one of the most studied parts of human genetics, but in a somewhat surprising organism--fruit flies (Drosophila melanogaster).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We have developed a new set of algorithms, collectively called "Velvet," to manipulate de Bruijn graphs for genomic sequence assembly. A de Bruijn graph is a compact representation based on short ...words (k-mers) that is ideal for high coverage, very short read (25-50 bp) data sets. Applying Velvet to very short reads and paired-ends information only, one can produce contigs of significant length, up to 50-kb N50 length in simulations of prokaryotic data and 3-kb N50 on simulated mammalian BACs. When applied to real Solexa data sets without read pairs, Velvet generated contigs of approximately 8 kb in a prokaryote and 2 kb in a mammalian BAC, in close agreement with our simulated results without read-pair information. Velvet represents a new approach to assembly that can leverage very short reads in combination with read pairs to produce useful assemblies.
RNA molecules undergo a vast array of chemical post-transcriptional modifications (PTMs) that can affect their structure and interaction properties. In recent years, a growing number of PTMs have ...been successfully mapped to the transcriptome using experimental approaches relying on high-throughput sequencing. Oxford Nanopore direct-RNA sequencing has been shown to be sensitive to RNA modifications. We developed and validated Nanocompore, a robust analytical framework that identifies modifications from these data. Our strategy compares an RNA sample of interest against a non-modified control sample, not requiring a training set and allowing the use of replicates. We show that Nanocompore can detect different RNA modifications with position accuracy in vitro, and we apply it to profile m
A in vivo in yeast and human RNAs, as well as in targeted non-coding RNAs. We confirm our results with orthogonal methods and provide novel insights on the co-occurrence of multiple modified residues on individual RNA molecules.
MOTIVATION: High-throughput sequencing has made the analysis of new model organisms more affordable. Although assembling a new genome can still be costly and difficult, it is possible to use RNA-seq ...to sequence mRNA. In the absence of a known genome, it is necessary to assemble these sequences de novo, taking into account possible alternative isoforms and the dynamic range of expression values. RESULTS: We present a software package named Oases designed to heuristically assemble RNA-seq reads in the absence of a reference genome, across a broad spectrum of expression values and in presence of alternative isoforms. It achieves this by using an array of hash lengths, a dynamic filtering of noise, a robust resolution of alternative splicing events and the efficient merging of multiple assemblies. It was tested on human and mouse RNA-seq data and is shown to improve significantly on the transABySS and Trinity de novo transcriptome assemblers. Availability and implementation: Oases is freely available under the GPL license at www.ebi.ac.uk/~zerbino/oases/ CONTACT: dzerbino@ucsc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Epigenome-wide association studies represent one means of applying genome-wide assays to identify molecular events that could be associated with human phenotypes. The epigenome is especially ...intriguing as a target for study, as epigenetic regulatory processes are, by definition, heritable from parent to daughter cells and are found to have transcriptional regulatory properties. As such, the epigenome is an attractive candidate for mediating long-term responses to cellular stimuli, such as environmental effects modifying disease risk. Such epigenomic studies represent a broader category of disease -omics, which suffer from multiple problems in design and execution that severely limit their interpretability. Here we define many of the problems with current epigenomic studies and propose solutions that can be applied to allow this and other disease -omics studies to achieve their potential for generating valuable insights.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Digital production, transmission and storage have revolutionized how we access and use information but have also made archiving an increasingly complex task that requires active, continuing ...maintenance of digital media. This challenge has focused some interest on DNA as an attractive target for information storage because of its capacity for high-density information encoding, longevity under easily achieved conditions and proven track record as an information bearer. Previous DNA-based information storage approaches have encoded only trivial amounts of information or were not amenable to scaling-up, and used no robust error-correction and lacked examination of their cost-efficiency for large-scale information archival. Here we describe a scalable method that can reliably store more information than has been handled before. We encoded computer files totalling 739 kilobytes of hard-disk storage and with an estimated Shannon information of 5.2 × 10(6) bits into a DNA code, synthesized this DNA, sequenced it and reconstructed the original files with 100% accuracy. Theoretical analysis indicates that our DNA-based storage scheme could be scaled far beyond current global information volumes and offers a realistic technology for large-scale, long-term and infrequently accessed digital archiving. In fact, current trends in technological advances are reducing DNA synthesis costs at a pace that should make our scheme cost-effective for sub-50-year archiving within a decade.
Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. ...After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure
. Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold
, at a scale that covers almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions that are likely to be disordered. Finally, we provide some case studies to illustrate how high-quality predictions could be used to generate biological hypotheses. We are making our predictions freely available to the community and anticipate that routine large-scale and high-accuracy structure prediction will become an important tool that will allow new questions to be addressed from a structural perspective.
Exhaustive methods of sequence alignment are accurate but slow, whereas heuristic approaches run quickly, but their complexity makes them more difficult to implement. We introduce bounded sparse ...dynamic programming (BSDP) to allow rapid approximation to exhaustive alignment. This is used within a framework whereby the alignment algorithms are described in terms of their underlying model, to allow automated development of efficient heuristic implementations which may be applied to a general set of sequence comparison problems.
The speed and accuracy of this approach compares favourably with existing methods. Examples of its use in the context of genome annotation are given.
This system allows rapid implementation of heuristics approximating to many complex alignment models, and has been incorporated into the freely available sequence alignment program, exonerate.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk/) provides freely available data and bioinformatics services to the scientific community, alongside its research ...activity and training provision. The 2020 COVID-19 pandemic has brought to the forefront a need for the scientific community to work even more cooperatively to effectively tackle a global health crisis. EMBL-EBI has been able to build on its position to contribute to the fight against COVID-19 in a number of ways. Firstly, EMBL-EBI has used its infrastructure, expertise and network of international collaborations to help build the European COVID-19 Data Platform (https://www.covid19dataportal.org/), which brings together COVID-19 biomolecular data and connects it to researchers, clinicians and public health professionals. By September 2020, the COVID-19 Data Platform has integrated in excess of 170 000 COVID-19 biomolecular data and literature records, collected through a number of EMBL-EBI resources. Secondly, EMBL-EBI has strived to continue its support of the life science communities through the crisis, with updated Training provision and improved service provision throughout its resources. The COVID-19 pandemic has highlighted the importance of EMBL-EBI’s core principles, including international cooperation, resource sharing and central data brokering, and has further empowered scientific cooperation.
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