DangerTrack: A scoring system to detect difficult-to-assess regions

Dolgalev, Igor; Sedlazeck, Fritz J.; Busby, Ben

doi:10.12688/f1000research.11254.1

Cited by 12 publications

(10 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S4). The short reads showed a few regions of extreme amplification (>100-fold) that were not detected by the long reads, although subsequent analysis showed these regions were highly enriched for low mappability regions (Dolgalev et al 2017) in the genome and therefore most likely to be mapping artifacts (Supplemental Fig. S5).…”

Section: Read Mapping and Copy Number Analysismentioning

confidence: 99%

Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

et al. 2018

View full text Add to dashboard Cite

The SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged, although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available, with nearly 20,000 variants present, most of which were missed by short-read sequencing. Surrounding the important oncogene (also known as), we discover a complex sequence of nested duplications and translocations, suggesting a punctuated progression. Full-length transcriptome sequencing further revealed several novel gene fusions within the nested genomic variants. Combining long-read genome and transcriptome sequencing enables an in-depth analysis of how SVs disrupt the genome and sheds new light on the complex mechanisms involved in cancer genome evolution.

show abstract

Section: Read Mapping and Copy Number Analysismentioning

confidence: 99%

Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Figures 3a-c show alignment rate and correctness stratified by the number of nonreference SNVs overlapped by a read. To obtain these subsets, we first removed reads originating from reference-genome regions deemed repetitive by DangerTrack [34] (score over 250). We did this after finding that these regions had a combination of low SNV density and repetitive content that caused the 0-SNV stratum to behave very differently from the others.…”

Section: Stratification By Variant Density Variant Rarity and Repetmentioning

confidence: 99%

FORGe: prioritizing variants for graph genomes

Pritt

Langmead

2018

Preprint

View full text Add to dashboard Cite

There is growing interest in using genetic variants to augment the reference genome into a "graph genome" to improve read alignment accuracy and reduce allelic bias. While adding a variant has the positive effect of removing an undesirable alignmentscore penalty, it also increases both the ambiguity of the reference genome and the cost of storing and querying the genome index. We introduce methods and a software tool called FORGe for modeling these effects and prioritizing variants accordingly. We show that FORGe enables a range of advantageous and measurable trade-offs between accuracy and computational overhead. more variation to the reference eventually reduces alignment accuracy. We suggest efficient models for scoring variants according to the effect on accuracy and "blowup" (computational overhead), and further show that these scores can be used to achieve a balance of accuracy and overhead superior to current approaches. For example, extrapolating to a whole-human DNA sequencing experiment at 40-fold average coverage, we estimate that a well-engineered augmented reference can yield about 4.8M more correctly aligned reads and 1.2M fewer incorrectly aligned compared to the linear reference. Our methods for selecting variants also reduce reference bias, a chief goals of graph genomes. Finally, we compare the accuracy yielded by our methods to that achieved using an ideal personalized graph genome. We show that our methods approach the ideal much more closely than both linear genomes -even when they are modified to contain only major allelesand graph genomes built on different sets of variants.These methods are implemented in a new open source software tool called FORGe. We demonstrate FORGe in conjunction with the HISAT2 [12] graph aligner and with another aligner based on the Enhanced Reference Genome [7]. But FORGe's models and methods are suitable for any aligner that can include variants in the reference.

show abstract

“…In the "constrained" model, to mimic the observed "geographical clustering" of breakpoints, a random percentage between 50 and 100% of breakpoints had to occur in the same chromosome while the remaining ones were free. As we know that some genomic regions are poorly analyzed for structural variants, we used the "DangerTrack" bed file (Dolgalev et al 2017) to exclude all breakpoints simulated in these regions and be comparable with the observed dataset. A single breakpoint of our in-house dataset overlaps the DangerTrack.…”

Section: Breakpoint Simulationmentioning

confidence: 99%

The enrichment of breakpoints in late-replicating chromatin provides novel insights into chromoanagenesis mechanisms

Chatron

Giannuzzi

Rollat‐Farnier

et al. 2020

Preprint

View full text Add to dashboard Cite

The rise of pangenomic molecular assays allowed uncovering complex rearrangements named chromoanagenesis that were hypothesized to result from catastrophic shattering events. Constitutional cases have typically been reported individually preventing identification of common features and uncovering the mechanisms at play. We characterized 20 new chromoanagenesis and discovered yet undescribed features. While literature differentiates chromothripsis and its shattering event repaired through non-homologous end joining from chromoanasynthesis born to aberrant replicative processes, we identified shattered chromosomes repaired through a combination of mechanisms. In particular, three samples present with rearrangement hubs comprising a fragmented kilobase-long sequence threaded throughout the rearrangement. To assess the mechanisms at play, we merged our data with those of 20 published constitutional complex chromosomal rearrangement cases. We evaluated if the distribution of their 1032 combined breakpoints was distinctive using bootstrap simulations and found that breakpoints tend to keep away from haplosensitive genes suggesting selective pressure. We then compared their distribution with that of 13,310 and 468 breakpoints of cancer complex chromosomal rearrangements and constitutional simple rearrangement samples, respectively. Both complex rearrangement groups showed breakpoint enrichment in late replicating regions suggesting similar origins for constitutional and cancer cases. Simple rearrangement breakpoints but not complex ones were depleted from lamina-associated domains (LADs), possibly as a consequence of reduced mobility of DNA ends bound to lamina. The enrichment of breakpoints in late-replicating chromatin for both constitutional and cancer chromoanagenesis provides an orthogonal support to the premature chromosome condensation hypothesis that was put forward to explain chromoanagenesis.

show abstract

DangerTrack: A scoring system to detect difficult-to-assess regions

Cited by 12 publications

References 8 publications

Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

FORGe: prioritizing variants for graph genomes

The enrichment of breakpoints in late-replicating chromatin provides novel insights into chromoanagenesis mechanisms

Contact Info

Product

Resources

About