More Like this

1. Reference-agnostic representation and visualization of pan-genomes

   https://doi.org/10.1186/s12859-021-04424-w  

   Liang, Qihua; Lonardi, Stefano (October 2021, BMC Bioinformatics)

   Abstract BackgroundThe pan-genome of a species is the union of the genes and non-coding sequences present in all individuals (cultivar, accessions, or strains) within that species. ResultsHere we introduce PGV, a reference-agnostic representation of the pan-genome of a species based on the notion of consensus ordering. Our experimental results demonstrate that PGV enables an intuitive, effective and interactive visualization of a pan-genome by providing a genome browser that can elucidate complex structural genomic variations. ConclusionsThe PGV software can be installed via conda or downloaded fromhttps://github.com/ucrbioinfo/PGV. The companion PGV browser athttp://pgv.cs.ucr.educan be tested using example bed tracks available from the GitHub page. 

   more » « less
2. Piikun: an information theoretic toolkit for analysis and visualization of species delimitation metric space

   https://doi.org/10.1186/s12859-024-05997-y  

   Sukumaran, Jeet; Meila, Marina (December 2024, BMC Bioinformatics)

   Abstract <bold>Background</bold>Existing software for comparison of species delimitation models do not provide a (true) metric or distance functions between species delimitation models, nor a way to compare these models in terms of relative clustering differences along a lattice of partitions. <bold>Results</bold>is a Python package for analyzing and visualizing species delimitation models in an information theoretic framework that, in addition to classic measures of information such as the entropy and mutual information [1], provides for the calculation of the Variation of Information (VI) criterion [2], a true metric or distance function for species delimitation models that is aligned with the lattice of partitions. <bold>Conclusions</bold>is available under the MIT license from its public repository (https://github.com/jeetsukumaran/piikun), and can be installed locally using the Python package manager ‘pip‘. 

   more » « less
3. STalign: Alignment of spatial transcriptomics data using diffeomorphic metric mapping

   https://doi.org/10.1038/s41467-023-43915-7  

   Clifton, Kalen; Anant, Manjari; Aihara, Gohta; Atta, Lyla; Aimiuwu, Osagie K.; Kebschull, Justus M.; Miller, Michael I.; Tward, Daniel; Fan, Jean (December 2023, Nature Communications)

   Abstract Spatial transcriptomics (ST) technologies enable high throughput gene expression characterization within thin tissue sections. However, comparing spatial observations across sections, samples, and technologies remains challenging. To address this challenge, we develop STalign to align ST datasets in a manner that accounts for partially matched tissue sections and other local non-linear distortions using diffeomorphic metric mapping. We apply STalign to align ST datasets within and across technologies as well as to align ST datasets to a 3D common coordinate framework. We show that STalign achieves high gene expression and cell-type correspondence across matched spatial locations that is significantly improved over landmark-based affine alignments. Applying STalign to align ST datasets of the mouse brain to the 3D common coordinate framework from the Allen Brain Atlas, we highlight how STalign can be used to lift over brain region annotations and enable the interrogation of compositional heterogeneity across anatomical structures. STalign is available as an open-source Python toolkit athttps://github.com/JEFworks-Lab/STalignand as Supplementary Software with additional documentation and tutorials available athttps://jef.works/STalign. 

   more » « less
4. A novel nonlinear dimension reduction approach to infer population structure for low-coverage sequencing data

   https://doi.org/10.1186/s12859-021-04265-7  

   Zhang, Miao; Liu, Yiwen; Zhou, Hua; Watkins, Joseph; Zhou, Jin (June 2021, BMC Bioinformatics)

   Abstract BackgroundLow-depth sequencing allows researchers to increase sample size at the expense of lower accuracy. To incorporate uncertainties while maintaining statistical power, we introduce to analyze population structure of low-depth sequencing data. ResultsThe method optimizes the choice of nonlinear transformations of dosages to maximize the Ky Fan norm of the covariance matrix. The transformation incorporates the uncertainty in calling between heterozygotes and the common homozygotes for loci having a rare allele and is more linear when both variants are common. ConclusionsWe apply to samples from two indigenous Siberian populations and reveal hidden population structure accurately using only a single chromosome. The package is available onhttps://github.com/yiwenstat/MCPCA_PopGen. 

   more » « less
5. Heterogeneous pseudobulk simulation enables realistic benchmarking of cell-type deconvolution methods

   https://doi.org/10.1186/s13059-024-03292-w  

   Hu, Mengying; Chikina, Maria (December 2024, Genome Biology)

   Abstract BackgroundComputational cell type deconvolution enables the estimation of cell type abundance from bulk tissues and is important for understanding tissue microenviroment, especially in tumor tissues. With rapid development of deconvolution methods, many benchmarking studies have been published aiming for a comprehensive evaluation for these methods. Benchmarking studies rely on cell-type resolved single-cell RNA-seq data to create simulated pseudobulk datasets by adding individual cells-types in controlled proportions. ResultsIn our work, we show that the standard application of this approach, which uses randomly selected single cells, regardless of the intrinsic difference between them, generates synthetic bulk expression values that lack appropriate biological variance. We demonstrate why and how the current bulk simulation pipeline with random cells is unrealistic and propose a heterogeneous simulation strategy as a solution. The heterogeneously simulated bulk samples match up with the variance observed in real bulk datasets and therefore provide concrete benefits for benchmarking in several ways. We demonstrate that conceptual classes of deconvolution methods differ dramatically in their robustness to heterogeneity with reference-free methods performing particularly poorly. For regression-based methods, the heterogeneous simulation provides an explicit framework to disentangle the contributions of reference construction and regression methods to performance. Finally, we perform an extensive benchmark of diverse methods across eight different datasets and find BayesPrism and a hybrid MuSiC/CIBERSORTx approach to be the top performers. ConclusionsOur heterogeneous bulk simulation method and the entire benchmarking framework is implemented in a user friendly packagehttps://github.com/humengying0907/deconvBenchmarkingandhttps://doi.org/10.5281/zenodo.8206516, enabling further developments in deconvolution methods. 

   more » « less