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Reinders, M.

Publications and source records attributed to Reinders, M..

2 recordsLinked to original sources

Predicting cell types in single cell mass cytometry data

MotivationMass cytometry (CyTOF) is a valuable technology for high-dimensional analysis at the single cell level. Identification of different cell populations is an important task during the data analysis. Many clustering tools can perform this task, however, they are time consuming, often involve a manual step, and lack reproducibility when new data is included in the analysis. Learning cell types from an annotated set of cells solves these problems. However, currently available mass cytometry classifiers are either complex, dependent on prior knowledge of the cell type markers during the learning process, or can only identify canonical cell types.\n\nResultsWe propose to use a Linear Discriminant Analysis (LDA) classifier to automatically identify cell populations in CyTOF data. LDA shows comparable results with two state-of-the-art algorithms on four benchmark datasets and also outperforms a non-linear classifier such as the k-nearest neighbour classifier. To illustrate its scalability to large datasets with deeply annotated cell subtypes, we apply LDA to a dataset of ~3.5 million cells representing 57 cell types. LDA has high performance on abundant cell types as well as the majority of rare cell types, and provides accurate estimates of cell type frequencies. Further incorporating a rejection option, based on the estimated posterior probabilities, allows LDA to identify cell types that were not encountered during training. Altogether, reproducible prediction of cell type compositions using LDA opens up possibilities to analyse large cohort studies based on mass cytometry data.\n\nAvailabilityImplementation is available on GitHub (https://github.com/tabdelaal/CyTOF-Linear-Classifier).\n\nContacta.mahfouz@lumc.nl

bioinformatics

CHOP: Haplotype-aware path indexing in population graphs

MotivationAlthough the characterization of within species genomic diversity continues to increase, this information is usually not incorporated in the sequencing analysis process. Existing reference genomes can easily be converted to graph-based reference genomes by extending them with known sequence variations. However, the practical use of these graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of increasing pattern length and encoded variations inevitably leads to a combinatorial explosion of the search space. We present a solution that uses haplotype information to prevent this from happening.\n\nResultsWe present CHOP, a method that uses haplotype information to retrieve the constrained sequence search space of a graph-based reference genome. Our approach enables typical sequence aligners to perform read alignments to graphs that store any type of variation. CHOP performs similarly to another graph alignment method that unnecessarily indexes all combinations of sequence, while aligning reads to a population reference graph of Mycobacterium tuberculosis genomes. CHOP can achieve increased sensitivity for variation detection by iteratively integrating variation into a graph. Finally, we show that CHOP can be applied to large and complex datasets, by applying it on a graph-based representation of chromosome 6 of the human genome encoding the variants reported by the 1000 Genomes project.

bioinformatics