Integration of intra-sample contextual error modeling for improved detection of somatic mutations
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001003806 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Sensitive mutation detection by next-generation sequencing is critical for early cancer detection, monitoring minimal/measurable residual disease (MRD), and guiding precision oncology. Nevertheless, because of artifacts introduced during library preparation and sequencing, the detection of low-frequency variants at high specificity is problematic. Here, we present Espresso, an error suppression method that considers local sequence features to accurately detect single-nucleotide variants (SNVs). Compared to other advanced error suppression techniques, Espresso consistently demonstrated lower numbers of false-positive mutation calls and greater sensitivity. We demonstrated Espresso's superior performance in detecting MRD in the peripheral blood of patients with acute myeloid leukemia (AML) throughout their treatment course. Furthermore, we showed that accurate mutation calling in a small number of informative genomic loci might provide a cost-efficient strategy for pragmatic risk prediction of AML development in healthy individuals. More broadly, we aim for Espresso to aid with accurate mutation detection in many other research and clinical settings.
| S-EPMC7725472 | biostudies-literature
Project description:Detection of somatic variation using sequence from disease-control matched data sets is a critical first step. In many cases including cancer, however, it is hard to isolate pure disease tissue, and the impurity hinders accurate mutation analysis by disrupting overall allele frequencies. Here, we propose a new method, Virmid, that explicitly determines the level of impurity in the sample, and uses it for improved detection of somatic variation. Extensive tests on simulated and real sequencing data from breast cancer and hemimegalencephaly demonstrate the power of our model. A software implementation of our method is available at http://sourceforge.net/projects/virmid/.
| S-EPMC4054681 | biostudies-literature
Project description:Abstract Identification of errors or anomalous values, collectively considered outliers, assists in exploring data or through removing outliers improves statistical analysis. In biomechanics, outlier detection methods have explored the ‘shape’ of the entire cycles, although exploring fewer points using a ‘moving-window’ may be advantageous. Hence, the aim was to develop a moving-window method for detecting trials with outliers in intra-participant time-series data. Outliers were detected through two stages for the strides (mean 38 cycles) from treadmill running. Cycles were removed in stage 1 for one-dimensional (spatial) outliers at each time point using the median absolute deviation, and in stage 2 for two-dimensional (spatial–temporal) outliers using a moving window standard deviation. Significance levels of the t-statistic were used for scaling. Fewer cycles were removed with smaller scaling and smaller window size, requiring more stringent scaling at stage 1 (mean 3.5 cycles removed for 0.0001 scaling) than at stage 2 (mean 2.6 cycles removed for 0.01 scaling with a window size of 1). Settings in the supplied Matlab code should be customised to each data set, and outliers assessed to justify whether to retain or remove those cycles. The method is effective in identifying trials with outliers in intra-participant time series data.
| S-EPMC7857460 | biostudies-literature
Project description:Somatic mutations are a primary contributor to malignancy in human cells. Accurate detection of mutations is needed to define the clonal composition of tumours whereby clones may have distinct phenotypic properties. Although analysis of mutations over multiple tumour samples from the same patient has the potential to enhance identification of clones, few analytic methods exploit the correlation structure across samples. We posited that incorporating clonal information into joint analysis over multiple samples would improve mutation detection, particularly those with low prevalence. In this paper, we develop a new procedure called MuClone, for detection of mutations across multiple tumour samples of a patient from whole genome or exome sequencing data. In addition to mutation detection, MuClone classifies mutations into biologically meaningful groups and allows us to study clonal dynamics. We show that, on lung and ovarian cancer datasets, MuClone improves somatic mutation detection sensitivity over competing approaches without compromising specificity.
| S-EPMC6355807 | biostudies-other
Project description:SummaryWe present Mutascope, a sequencing analysis pipeline specifically developed for the identification of somatic variants present at low-allelic fraction from high-throughput sequencing of amplicons from matched tumor-normal specimen. Using datasets reproducing tumor genetic heterogeneity, we demonstrate that Mutascope has a higher sensitivity and generates fewer false-positive calls than tools designed for shotgun sequencing or diploid genomes.AvailabilityFreely available on the web at http://sourceforge.net/projects/mutascope/.Contactoharismendy@ucsd.eduSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC3712217 | biostudies-literature
Project description:Detection of Somatic Mutations in vitro Aging Cells
| PRJNA554709 | ENA
Project description:Detection of Somatic Mutations in vitro Aging Cells
| PRJNA554710 | ENA
Project description:Due to lack of normal samples in clinical diagnosis and to reduce costs, detection of small-scale mutations from tumor-only samples is required but remains relatively unexplored. We developed an algorithm (GATKcan) augmenting GATK with two statistics and machine learning to detect mutations in cancer. The averaged performance of GATKcan in ten experiments outperformed GATK in detecting mutations of randomly sampled 231 from 241 TCGA endometrial tumors (EC). In external validations, GATKcan outperformed GATK in TCGA breast cancer (BC), ovarian cancer (OC) and melanoma tumors, in terms of Matthews correlation coefficient (MCC) and precision, where MCC takes both sensitivity and specificity into account. Further, GATKcan reduced high fractions of false positives detected by GATK. In mutation detection of somatic variants, classified commonly by VarScan 2 and MuTect from the called variants in BC, OC and melanoma, ranked by adjusted MCC (adjusted precision) GATKcan was the top 1, followed by MuTect, VarScan 2 and GATK. Importantly, GATKcan enables detection of mutations when alternate alleles exist in normal samples. These results suggest that GATKcan trained by a cancer is able to detect mutations in future patients with the same type of cancer and is likely applicable to other cancers with similar mutations.
| S-EPMC5698426 | biostudies-literature
Project description:Fraud detection through auditors' manual review of accounting and financial records has traditionally relied on human experience and intuition. However, replicating this task using technological tools has represented a challenge for information security researchers. Natural language processing techniques, such as topic modeling, have been explored to extract information and categorize large sets of documents. Topic modeling, such as latent Dirichlet allocation (LDA) or non-negative matrix factorization (NMF), has recently gained popularity for discovering thematic structures in text collections. However, unsupervised topic modeling may not always produce the best results for specific tasks, such as fraud detection. Therefore, in the present work, we propose to use semi-supervised topic modeling, which allows the incorporation of specific knowledge of the study domain through the use of keywords to learn latent topics related to fraud. By leveraging relevant keywords, our proposed approach aims to identify patterns related to the vertices of the fraud triangle theory, providing more consistent and interpretable results for fraud detection. The model's performance was evaluated by training with several datasets and testing it with another one that did not intervene in its training. The results showed efficient performance averages with a 7% increase in performance compared to a previous job. Overall, the study emphasizes the importance of deepening the analysis of fraud behaviors and proposing strategies to identify them proactively.
| S-EPMC10803081 | biostudies-literature
Project description:Detection of somatic point substitutions is a key step in characterizing the cancer genome. However, existing methods typically miss low-allelic-fraction mutations that occur in only a subset of the sequenced cells owing to either tumor heterogeneity or contamination by normal cells. Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. We also describe benchmarking approaches that use real, rather than simulated, sequencing data to evaluate the sensitivity and specificity as a function of sequencing depth, base quality and allelic fraction. Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data.
| S-EPMC3833702 | biostudies-literature