| 1. |
- Bradnam, K. R., et al.
(författare)
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Assemblathon 2 : Evaluating de novo methods of genome assembly in three vertebrate species
- 2013
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Ingår i: GigaScience. - : BioMed Central (BMC). - 2047-217X. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.
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| 2. |
- Eisfeldt, J., et al.
(författare)
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Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements
- 2019
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Ingår i: PLOS Genetics. - : NLM (Medline). - 1553-7390 .- 1553-7404. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. We have studied three individuals with CCRs: Case 1 and Case 2 presented with de novo karyotypically balanced, complex interchromosomal rearrangements (46,XX,t(2;8;15)(q35;q24.1;q22) and 46,XY,t(1;10;5)(q32;p12;q31)), and Case 3 presented with a de novo, extremely complex intrachromosomal rearrangement on chromosome 1. Molecular cytogenetic investigation revealed cryptic deletions in the breakpoints of chromosome 2 and 8 in Case 1, and on chromosome 10 in Case 2, explaining their clinical symptoms. In Case 3, 26 breakpoints were identified using WGS, disrupting five known disease genes. All rearrangements were subsequently analyzed using optical maps, linked-read WGS, and short-read WGS. In conclusion, we present a case series of three unique de novo CCRs where we by combining the results from the different technologies fully solved the structure of each rearrangement. The power in combining short-read WGS with long-molecule sequencing or optical mapping in these unique de novo CCRs in a clinical setting is demonstrated.
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| 3. |
- Eisfeldt, J, et al.
(författare)
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TIDDIT, an efficient and comprehensive structural variant caller for massive parallel sequencing data
- 2017
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Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402. ; 6, s. 664-
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Tidskriftsartikel (refereegranskat)abstract
- Reliable detection of large structural variation ( > 1000 bp) is important in both rare and common genetic disorders. Whole genome sequencing (WGS) is a technology that may be used to identify a large proportion of the genomic structural variants (SVs) in an individual in a single experiment. Even though SV callers have been extensively used in research to detect mutations, the potential usage of SV callers within routine clinical diagnostics is still limited. One well known, but not well-addressed problem is the large number of benign variants and reference errors present in the human genome that further complicates analysis. Even though there is a wide range of SV-callers available, the number of callers that allow detection of the entire spectra of SV at a low computational cost is still relatively limited.
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| 5. |
- Nadalin, F., et al.
(författare)
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A multi-objective optimisation approach to the design of experiment in de novo assembly projects
- 2012
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Ingår i: Database and Expert Systems Applications (DEXA), 2012 23rd International Workshop on. - : IEEE. - 9780769548012 ; , s. 213-217
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Konferensbidrag (refereegranskat)abstract
- Genomics projects are characterised by difficult biological pipelines and high sequencing costs. In particular, de novo assembly projects must go through data production, assembly, and results validation. Early mistakes in the first (and most expensive) step can therefore be detected only at a very late stage and have serious consequences. Our goal is to design a pipeline able to provide the users with the optimal input for the sequencing experiments within a de novo assembly project. We present a new approach, based on multi-objective optimisation, aiming at transforming the design of genomics experiments from a set of "best practices" to an algorithmically controlled procedure. We implemented our model with mode FRONTIER and we show how our method can be used to infer the final quality of a whole genome assembly project from the results obtained on a small but representative sample.
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