Dataset Information

OutLyzer: software for extracting low-allele-frequency tumor mutations from sequencing background noise in clinical practice.

ABSTRACT: Highlighting tumoral mutations is a key step in oncology for personalizing care. Considering the genetic heterogeneity in a tumor, software used for detecting mutations should clearly distinguish real tumor events of interest that could be predictive markers for personalized medicine from false positives. OutLyzer is a new variant-caller designed for the specific and sensitive detection of mutations for research and diagnostic purposes. It is based on statistic and local evaluation of sequencing background noise to highlight potential true positive variants. 130 previously genotyped patients were sequenced after enrichment by capturing the exons of 22 genes. Sequencing data were analyzed by HaplotypeCaller, LofreqStar, Varscan2 and OutLyzer. OutLyzer had the best sensitivity and specificity with a fixed limit of detection for all tools of 1% for SNVs and 2% for Indels. OutLyzer is a useful tool for detecting mutations of interest in tumors including low allele-frequency mutations, and could be adopted in standard practice for delivering targeted therapies in cancer treatment.

SUBMITTER: Muller E

PROVIDER: S-EPMC5346729 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

OutLyzer: software for extracting low-allele-frequency tumor mutations from sequencing background noise in clinical practice.

Muller Etienne E Goardon Nicolas N Brault Baptiste B Rousselin Antoine A Paimparay Germain G Legros Angelina A Fouillet Robin R Bruet Olivia O Tranchant Aurore A Domin Florian F San Chankannira C Quesnelle Céline C Frebourg Thierry T Ricou Agathe A Krieger Sophie S Vaur Dominique D Castera Laurent L

Oncotarget 20161101 48

Highlighting tumoral mutations is a key step in oncology for personalizing care. Considering the genetic heterogeneity in a tumor, software used for detecting mutations should clearly distinguish real tumor events of interest that could be predictive markers for personalized medicine from false positives. OutLyzer is a new variant-caller designed for the specific and sensitive detection of mutations for research and diagnostic purposes. It is based on statistic and local evaluation of sequencing ...[more]

PMID: 27825131

Similar Datasets

Project description:Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across approximately 500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the "American Modal Haplotype" (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population that may have been isolated from other Asian populations prior to expanding into the Americas.

Project description:Frequency modulated continuous wave laser ranging (FMCW LiDAR) enables distance mapping with simultaneous position and velocity information, is immune to stray light, can achieve long range, operate in the eye-safe region of 1550 nm and achieve high sensitivity. Despite its advantages, it is compounded by the simultaneous requirement of both narrow linewidth low noise lasers that can be precisely chirped. While integrated silicon-based lasers, compatible with wafer scale manufacturing in large volumes at low cost, have experienced major advances and are now employed on a commercial scale in data centers, and impressive progress has led to integrated lasers with (ultra) narrow sub-100 Hz-level intrinsic linewidth based on optical feedback from photonic circuits, these lasers presently lack fast nonthermal tuning, i.e. frequency agility as required for coherent ranging. Here, we demonstrate a hybrid photonic integrated laser that exhibits very narrow intrinsic linewidth of 25 Hz while offering linear, hysteresis-free, and mode-hop-free-tuning beyond 1 GHz with up to megahertz actuation bandwidth constituting 1.6 × 1015 Hz/s tuning speed. Our approach uses foundry-based technologies - ultralow-loss (1 dB/m) Si3N4 photonic microresonators, combined with aluminium nitride (AlN) or lead zirconium titanate (PZT) microelectromechanical systems (MEMS) based stress-optic actuation. Electrically driven low-phase-noise lasing is attained by self-injection locking of an Indium Phosphide (InP) laser chip and only limited by fundamental thermo-refractive noise at mid-range offsets. By utilizing difference-drive and apodization of the photonic chip to suppress mechanical vibrations of the chip, a flat actuation response up to 10 MHz is achieved. We leverage this capability to demonstrate a compact coherent LiDAR engine that can generate up to 800 kHz FMCW triangular optical chirp signals, requiring neither any active linearization nor predistortion compensation, and perform a 10 m optical ranging experiment, with a resolution of 12.5 cm. Our results constitute a photonic integrated laser system for scenarios where high compactness, fast frequency actuation, and high spectral purity are required.

Dataset Information

OutLyzer: software for extracting low-allele-frequency tumor mutations from sequencing background noise in clinical practice.

Publications

OutLyzer: software for extracting low-allele-frequency tumor mutations from sequencing background noise in clinical practice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets