Copy number aberrations (CNAs) are ubiquitous in many types of cancer. Inferring CNAs from cancer genomic data could help shed light on the initiation, progression, and potential treatment of cancer. While such data have traditionally been available via “bulk sequencing,” the more recently introduced techniques for single-cell DNA sequencing (scDNAseq) provide the type of data that makes CNA inference possible at the single-cell resolution. We introduce a new birth-death evolutionary model of CNAs and a Bayesian method, NestedBD, for the inference of evolutionary trees (topologies and branch lengths with relative mutation rates) from single-cell data. We evaluated NestedBD’s performance using simulated data sets, benchmarking its accuracy against traditional phylogenetic tools as well as state-of-the-art methods. The results show that NestedBD infers more accurate topologies and branch lengths, and that the birth-death model can improve the accuracy of copy number estimation. And when applied to biological data sets, NestedBD infers plausible evolutionary histories of two colorectal cancer samples. NestedBD is available at
In this paper, we present the disjunctive Bayesian network (DBN), a novel oncogenetic model with a phylogenetic interpretation. DBN is expressive enough to capture cancer subtypes' trajectories and mutually exclusive relations between alterations from unstratified data.
- NSF-PAR ID:
- 10389000
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Computational and Systems Oncology
- Volume:
- 1
- Issue:
- 2
- ISSN:
- 2689-9655
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract https://github.com/Androstane/NestedBD . -
more » « less
Abstract Genomic profiles of cancer cells provide valuable information on genetic alterations in cancer. Several recent studies employed these data to predict the response of cancer cell lines to drug treatment. Nonetheless, due to the multifactorial phenotypes and intricate mechanisms of cancer, the accurate prediction of the effect of pharmacotherapy on a specific cell line based on the genetic information alone is problematic. Emphasizing on the system-level complexity of cancer, we devised a procedure to integrate multiple heterogeneous data, including biological networks, genomics, inhibitor profiling, and gene-disease associations, into a unified graph structure. In order to construct compact, yet information-rich cancer-specific networks, we developed a novel graph reduction algorithm. Driven by not only the topological information, but also the biological knowledge, the graph reduction increases the feature-only entropy while preserving the valuable graph-feature information. Subsequent comparative benchmarking simulations employing a tissue level cross-validation protocol demonstrate that the accuracy of a graph-based predictor of the drug efficacy is 0.68, which is notably higher than those measured for more traditional, matrix-based techniques on the same data. Overall, the non-Euclidean representation of the cancer-specific data improves the performance of machine learning to predict the response of cancer to pharmacotherapy. The generated data are freely available to the academic community at
https://osf.io/dzx7b/ . -
more » « less
Abstract Computational workflows are widely used in data analysis, enabling automated tracking of steps and storage of provenance information, leading to innovation and decision-making in the scientific community. However, the growing popularity of workflows has raised concerns about reproducibility and reusability which can hinder collaboration between institutions and users. In order to address these concerns, it is important to standardize workflows or provide tools that offer a framework for describing workflows and enabling computational reusability. One such set of standards that has recently emerged is the Common Workflow Language (CWL), which offers a robust and flexible framework for data analysis tools and workflows. To promote portability, reproducibility, and interoperability of AI/ML workflows, we developed
geoweaver_cwl geoweaver_cwl geoweaver_cwl https://pypi.org/project/geoweaver-cwl/0.0.1/ and exemplar results are accessible at:https://github.com/amrutakale08/geoweaver_cwl-usecases . -
more » « less
Abstract Background Differential correlation networks are increasingly used to delineate changes in interactions among biomolecules. They characterize differences between omics networks under two different conditions, and can be used to delineate mechanisms of disease initiation and progression.
Results We present a new R package, , that facilitates the estimation and visualization of differential correlation networks using multiple correlation measures and inference methods. The software is implemented in , and , and is available at
https://github.com/sqyu/CorDiffViz . Visualization has been tested for the Chrome and Firefox web browsers. A demo is available athttps://diffcornet.github.io/CorDiffViz/demo.html .Conclusions Our software offers considerable flexibility by allowing the user to interact with the visualization and choose from different estimation methods and visualizations. It also allows the user to easily toggle between correlation networks for samples under one condition and differential correlations between samples under two conditions. Moreover, the software facilitates integrative analysis of cross-correlation networks between two omics data sets.
-
more » « less
Abstract We present a new method and software tool called that applies a pangenome index to the problem of inferring genotypes from short-read sequencing data. The method uses a novel indexing structure called the marker array. Using the marker array, we can genotype variants with respect from large panels like the 1000 Genomes Project while reducing the reference bias that results when aligning to a single linear reference. can infer accurate genotypes in less time and memory compared to existing graph-based methods. The method is implemented in the open source software tool available at
https://github.com/alshai/rowbowt .
