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1. ViralMSA: massively scalable reference-guided multiple sequence alignment of viral genomes

   https://doi.org/10.1093/bioinformatics/btaa743  

   Moshiri, Niema (August 2020, Bioinformatics)

   Robinson, Peter (Ed.)

   Abstract Motivation In molecular epidemiology, the identification of clusters of transmissions typically requires the alignment of viral genomic sequence data. However, existing methods of multiple sequence alignment (MSA) scale poorly with respect to the number of sequences. Results ViralMSA is a user-friendly reference-guided MSA tool that leverages the algorithmic techniques of read mappers to enable the MSA of ultra-large viral genome datasets. It scales linearly with the number of sequences, and it is able to align tens of thousands of full viral genomes in seconds. However, alignments produced by ViralMSA omit insertions with respect to the reference genome. Availability and implementation ViralMSA is freely available at https://github.com/niemasd/ViralMSA as an open-source software project. Contact niema@ucsd.edu Supplementary information Supplementary data are available at Bioinformatics online. 

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2. Detecting and correcting misclassified sequences in the large-scale public databases

   https://doi.org/10.1093/bioinformatics/btaa586  

   Bagheri, Hamid; Severin, Andrew; Rajan, Hridesh; Elofsson, Arne (June 2020, Bioinformatics)

   Abstract Motivation As the cost of sequencing decreases, the amount of data being deposited into public repositories is increasing rapidly. Public databases rely on the user to provide metadata for each submission that is prone to user error. Unfortunately, most public databases, such as non-redundant (NR), rely on user input and do not have methods for identifying errors in the provided metadata, leading to the potential for error propagation. Previous research on a small subset of the non-redundant (NR) database analyzed misclassification based on sequence similarity. To the best of our knowledge, the amount of misclassification in the entire database has not been quantified. We propose a heuristic method to detect potentially misclassified taxonomic assignments in the NR database. We applied a curation technique and quality control to find the most probable taxonomic assignment. Our method incorporates provenance and frequency of each annotation from manually and computationally created databases and clustering information at 95% similarity. Results We found more than 2 million potentially taxonomically misclassified proteins in the NR database. Using simulated data, we show a high precision of 97% and a recall of 87% for detecting taxonomically misclassified proteins. The proposed approach and findings could also be applied to other databases. Availability Source code, dataset, documentation, Jupyter notebooks, and Docker container are available at https://github.com/boalang/nr. Supplementary information Supplementary data are available at Bioinformatics online. 

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3. Plant 3D (P3D): a plant phenotyping toolkit for 3D point clouds

   https://doi.org/10.1093/bioinformatics/btaa220  

   Ziamtsov, Illia; Navlakha, Saket (March 2020, Bioinformatics)

   Xu, Jinbo (Ed.)

   Abstract Motivation Developing methods to efficiently analyze 3D point cloud data of plant architectures remain challenging for many phenotyping applications. Here, we describe a tool that tackles four core phenotyping tasks: classification of cloud points into stem and lamina points, graph skeletonization of the stem points, segmentation of individual lamina and whole leaf labeling. These four tasks are critical for numerous downstream phenotyping goals, such as quantifying plant biomass, performing morphological analyses of plant shapes and uncovering genotype to phenotype relationships. The Plant 3D tool provides an intuitive graphical user interface, a fast 3D rendering engine for visualizing plants with millions of cloud points, and several graph-theoretic and machine-learning algorithms for 3D architecture analyses. Availability and implementation P3D is open-source and implemented in C++. Source code and Windows installer are freely available at https://github.com/iziamtso/P3D/. Contact iziamtso@ucsd.edu or navlakha@cshl.edu Supplementary information Supplementary data are available at Bioinformatics online. 

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4. DCI: learning causal differences between gene regulatory networks

   https://doi.org/10.1093/bioinformatics/btab167  

   Belyaeva, Anastasiya; Squires, Chandler; Uhler, Caroline (March 2021, Bioinformatics)

   Cowen, Lenore (Ed.)

   Abstract Summary Designing interventions to control gene regulation necessitates modeling a gene regulatory network by a causal graph. Currently, large-scale gene expression datasets from different conditions, cell types, disease states, and developmental time points are being collected. However, application of classical causal inference algorithms to infer gene regulatory networks based on such data is still challenging, requiring high sample sizes and computational resources. Here, we describe an algorithm that efficiently learns the differences in gene regulatory mechanisms between different conditions. Our difference causal inference (DCI) algorithm infers changes (i.e. edges that appeared, disappeared, or changed weight) between two causal graphs given gene expression data from the two conditions. This algorithm is efficient in its use of samples and computation since it infers the differences between causal graphs directly without estimating each possibly large causal graph separately. We provide a user-friendly Python implementation of DCI and also enable the user to learn the most robust difference causal graph across different tuning parameters via stability selection. Finally, we show how to apply DCI to single-cell RNA-seq data from different conditions and cell states, and we also validate our algorithm by predicting the effects of interventions. Availability and implementation Python package freely available at http://uhlerlab.github.io/causaldag/dci. Supplementary information Supplementary data are available at Bioinformatics online. 

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5. CLUE: exact maximal reduction of kinetic models by constrained lumping of differential equations

   https://doi.org/10.1093/bioinformatics/btab010  

   Ovchinnikov, Alexey; Pérez Verona, Isabel; Pogudin, Gleb; Tribastone, Mirco (February 2021, Bioinformatics)

   Valencia, Alfonso (Ed.)

   Abstract Motivation Detailed mechanistic models of biological processes can pose significant challenges for analysis and parameter estimations due to the large number of equations used to track the dynamics of all distinct configurations in which each involved biochemical species can be found. Model reduction can help tame such complexity by providing a lower-dimensional model in which each macro-variable can be directly related to the original variables. Results We present CLUE, an algorithm for exact model reduction of systems of polynomial differential equations by constrained linear lumping. It computes the smallest dimensional reduction as a linear mapping of the state space such that the reduced model preserves the dynamics of user-specified linear combinations of the original variables. Even though CLUE works with non-linear differential equations, it is based on linear algebra tools, which makes it applicable to high-dimensional models. Using case studies from the literature, we show how CLUE can substantially lower model dimensionality and help extract biologically intelligible insights from the reduction. Availabilityand implementation An implementation of the algorithm and relevant resources to replicate the experiments herein reported are freely available for download at https://github.com/pogudingleb/CLUE. Supplementary information Supplementary data are available at Bioinformatics online. 

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