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1.
Cell Syst ; 10(4): 323-332.e8, 2020 04 22.
Article in English | MEDLINE | ID: mdl-32864481

ABSTRACT

A small number of somatic mutations drive the development of cancer, but all somatic mutations are markers of the evolutionary history of a tumor. Prominent methods to construct phylogenies from single-cell sequencing data use single-nucleotide variants (SNVs) as markers but fail to adequately account for copy-number aberrations (CNAs), which can overlap SNVs and result in SNV losses. Here, we introduce SCARLET, an algorithm that infers tumor phylogenies from single-cell DNA sequencing data while accounting for both CNA-driven loss of SNVs and sequencing errors. SCARLET outperforms existing methods on simulated data, with more accurate inference of the order in which mutations were acquired and the mutations present in individual cells. Using a single-cell dataset from a patient with colorectal cancer, SCARLET constructs a tumor phylogeny that is consistent with the observed CNAs and suggests an alternate origin for the patient's metastases. SCARLET is available at: github.com/raphael-group/scarlet.


Subject(s)
Neoplasms/genetics , Sequence Analysis, DNA/methods , Single-Cell Analysis/methods , Algorithms , DNA Copy Number Variations/genetics , Humans , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics
2.
IEEE Trans Big Data ; 5(2): 109-119, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31240237

ABSTRACT

Since the BRAIN Initiative and Human Brain Project began, a few efforts have been made to address the computational challenges of neuroscience Big Data. The promises of these two projects were to model the complex interaction of brain and behavior and to understand and diagnose brain diseases by collecting and analyzing large quanitites of data. Archiving, analyzing, and sharing the growing neuroimaging datasets posed major challenges. New computational methods and technologies have emerged in the domain of Big Data but have not been fully adapted for use in neuroimaging. In this work, we introduce the current challenges of neuroimaging in a big data context. We review our efforts toward creating a data management system to organize the large-scale fMRI datasets, and present our novel algorithms/methods for the distributed fMRI data processing that employs Hadoop and Spark. Finally, we demonstrate the significant performance gains of our algorithms/methods to perform distributed dictionary learning.

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