Biology subjects

Baker, D. N.

Publications and source records attributed to Baker, D. N..

4 recordsLinked to original sources

bioRxiv2022

A scalable and unbiased discordance metric with H+

A standard unsupervised analysis is to cluster observations into discrete groups using a dissimilarity measure, such as Euclidean distance. If there does not exist a ground-truth label for each observation necessary for external validity metrics, then internal validity metrics, such as the tightness or consistency of the cluster, are often used. However, the interpretation of these internal metrics can be problematic when using different dissimilarity measures as they have different magnitudes and ranges of values that they span. To address this problem, previous work introduced the scale-agnostic G+ discordance metric, however this internal metric is slow to calculate for large data. Furthermore, we show that G+ varies as a function of the proportion of observations in the predicted cluster labels (group balance), which is an undesirable property. To address this problem, we propose a modification of G+, referred to as H+, and demonstrate that H+ does not vary as a function of group balance using a simulation study and with public single-cell RNA-sequencing data. Finally, we provide scalable approaches to estimate H+, which are available in the fasthplus R package.

bioinformatics↗

bioRxiv2021

minicore: Fast scRNA-seq clustering with various distance measures

Single-cell RNA-sequencing (scRNA-seq) analyses typically begin by clustering a gene-by-cell expression matrix to empirically define groups of cells with similar expression profiles. We describe new methods and a new open source library, minicore, for efficient k-means++ center finding and k-means clustering of scRNA-seq data. Minicore works with sparse count data, as it emerges from typical scRNA-seq experiments, as well as with dense data from after dimensionality reduction. Minicores novel vectorized weighted reservoir sampling algorithm allows it to find initial k-means++ centers for a 4-million cell dataset in 1.5 minutes using 20 threads. Minicore can cluster using Euclidean distance, but also supports a wider class of measures like Jensen-Shannon Divergence, Kullback-Leibler Divergence, and the Bhattacharyya distance, which can be directly applied to count data and probability distributions. Further, minicore produces lower-cost centerings more efficiently than scikit-learn for scRNA-seq datasets with millions of cells. With careful handling of priors, minicore implements these distance measures with only minor (<2-fold) speed differences among all distances. We show that a minicore pipeline consisting of k-means++, localsearch++ and minibatch k-means can cluster a 4-million cell dataset in minutes, using less than 10GiB of RAM. This memory-efficiency enables atlas-scale clustering on laptops and other commodity hardware. Finally, we report findings on which distance measures give clusterings that are most consistent with known cell type labels. AvailabilityThe open source library is at https://github.com/dnbaker/minicore. Code used for experiments is at https://github.com/dnbaker/minicore-experiments.

bioinformatics↗

bioRxiv2020

Megadepth: efficient coverage quantification for BigWigs and BAMs

MotivationA common way to summarize sequencing datasets is to quantify data lying within genes or other genomic intervals. This can be slow and can require different tools for different input file types. ResultsMegadepth is a fast tool for quantifying alignments and coverage for BigWig and BAM/CRAM input files, using substantially less memory than the next-fastest competitor. Megadepth can summarize coverage within all disjoint intervals of the Gencode V35 gene annotation for more than 19,000 GTExV8 BigWig files in approximately one hour using 32 threads. Megadepth is available both as a command-line tool and as an R/Bioconductor package providing much faster quantification compared to the rtracklayer package. Availabilityhttps://github.com/ChristopherWilks/megadepth, https://bioconductor.org/packages/megadepth. Contactchris.wilks@jhu.edu

bioinformatics↗

bioRxiv2018

Dashing: Fast and Accurate Genomic Distances with HyperLogLog

Dashing is a fast and accurate software tool for estimating similarities of genomes or sequencing datasets. It uses the HyperLogLog sketch together with cardinality estimation methods that are specialized for set unions and intersections. Dashing summarizes genomes more rapidly than previous MinHash-based methods while providing greater accuracy across a wide range of input sizes and sketch sizes. It can sketch and calculate pairwise distances for over 87K genomes in 6 minutes. Dashing is open source and available at https://github.com/dnbaker/dashing.

bioinformatics↗