Most downloaded biology preprints, all time
in category bioinformatics
9,441 results found. For more information, click each entry to expand.
83,888 downloads bioRxiv bioinformatics
The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. The phylogeny of the genomes yields some interesting results. Systematic gene level mutational analysis of the genomes has enabled us to identify several unique features of the SARS-CoV2 genome, which includes a unique mutation in the spike surface glycoprotein (A930V (24351C>T)) in the Indian SARS-CoV2, absent in other strains studied here. We have also predicted the impact of the mutations in the spike glycoprotein function and stability, using computational approach. To gain further insights into host responses to viral infection, we predict that antiviral host-miRNAs may be controlling the viral pathogenesis. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Interestingly, the nine miRNAs do not have targets in SARS and MERS genomes. Also, hsa-miR-27b is the only unique miRNA which has a target gene in the Indian SARS-CoV2 genome. We also predicted immune epitopes in the genomes.
63,564 downloads bioRxiv bioinformatics
A novel coronavirus SARS-CoV-2 was identified in Wuhan, Hubei Province, China in December of 2019. According to WHO report, this new coronavirus has resulted in 76,392 confirmed infections and 2,348 deaths in China by 22 February, 2020, with additional patients being identified in a rapidly growing number internationally. SARS-CoV-2 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral entry, reproduction and transmission. This study provides a biological background for the epidemic investigation of the COVID-19, and could be informative for future anti-ACE2 therapeutic strategy development. ### Competing Interest Statement The authors have declared no competing interest.
54,201 downloads bioRxiv bioinformatics
Travers Ching, Daniel S. Himmelstein, Brett K Beaulieu-Jones, Alexandr A. Kalinin, BT Do, Gregory P. Way, Enrico Ferrero, Paul-Michael Agapow, Michael Zietz, Michael M. Hoffman, Wei Xie, Gail Rosen, Benjamin J. Lengerich, Johnny Israeli, Jack Lanchantin, Stephen Woloszynek, Anne E. Carpenter, Avanti Shrikumar, Jinbo Xu, Evan M. Cofer, Christopher A. Lavender, Srinivas C Turaga, Amr Alexandari, Zhiyong Lu, David J. Harris, Dave DeCapprio, Yanjun Qi, Anshul Kundaje, Yifan Peng, Laura K Wiley, Marwin H.S. Segler, Simina M. Boca, S.J. Swamidass, Austin Huang, Anthony Gitter, Casey S Greene
Deep learning, which describes a class of machine learning algorithms, has recently showed impressive results across a variety of domains. Biology and medicine are data rich, but the data are complex and often ill-understood. Problems of this nature may be particularly well-suited to deep learning techniques. We examine applications of deep learning to a variety of biomedical problems - patient classification, fundamental biological processes, and treatment of patients - and discuss whether deep learning will transform these tasks or if the biomedical sphere poses unique challenges. We find that deep learning has yet to revolutionize or definitively resolve any of these problems, but promising advances have been made on the prior state of the art. Even when improvement over a previous baseline has been modest, we have seen signs that deep learning methods may speed or aid human investigation. More work is needed to address concerns related to interpretability and how to best model each problem. Furthermore, the limited amount of labeled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning powering changes at both bench and bedside with the potential to transform several areas of biology and medicine.
33,139 downloads bioRxiv bioinformatics
Third-generation long-range DNA sequencing and mapping technologies are creating a renaissance in high-quality genome sequencing. Unlike second-generation sequencing, which produces short reads a few hundred base-pairs long, third-generation single-molecule technologies generate over 10,000 bp reads or map over 100,000 bp molecules. We analyze how increased read lengths can be used to address long-standing problems in de novo genome assembly, structural variation analysis and haplotype phasing.
23,729 downloads bioRxiv bioinformatics
We introduce Salmon, a new method for quantifying transcript abundance from RNA-seq reads that is highly-accurate and very fast. Salmon is the first transcriptome-wide quantifier to model and correct for fragment GC content bias, which we demonstrate substantially improves the accuracy of abundance estimates and the reliability of subsequent differential expression analysis compared to existing methods that do not account for these biases. Salmon achieves its speed and accuracy by combining a new dual-phase parallel inference algorithm and feature-rich bias models with an ultra-fast read mapping procedure. These innovations yield both exceptional accuracy and order-of-magnitude speed benefits over alignment-based methods.
19,915 downloads bioRxiv bioinformatics
In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq data, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data. DESeq2 uses shrinkage estimation for dispersions and fold changes to improve stability and interpretability of the estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression and facilitates downstream tasks such as gene ranking and visualization. DESeq2 is available as an R/Bioconductor package.
18,917 downloads bioRxiv bioinformatics
Christoph Muus, MD Luecken, Gokcen Eraslan, Avinash Waghray, Graham Heimberg, Lisa Sikkema, Yoshihiko Kobayashi, Eeshit Dhaval Vaishnav, Ayshwarya Subramanian, Christopher Smilie, Karthik Jagadeesh, Elizabeth Thu Duong, Evgenij Fiskin, Elena Torlai Triglia, Meshal Ansari, Peiwen Cai, Brian Lin, Justin Buchanan, Sijia Chen, Jian Shu, Adam L. Haber, Hattie Chung, Daniel T Montoro, Taylor Adams, Hananeh Aliee, J. Samuel, Allon Zaneta Andrusivova, Ilias Angelidis, Orr Ashenberg, Kevin Bassler, Christophe Bécavin, Inbal Benhar, Joseph Bergenstråhle, Ludvig Bergenstråhle, Liam Bolt, Emelie Braun, Linh T Bui, Mark Chaffin, Evgeny Chichelnitskiy, Joshua Chiou, Thomas M Conlon, Michael S Cuoco, Marie Deprez, David S. Fischer, Astrid Gillich, Joshua Gould, Minzhe Guo, Austin J Gutierrez, Arun C Habermann, Tyler Harvey, Peng He, Xiaomeng Hou, Lijuan Hu, Alok Jaiswal, Peiyong Jiang, Theodoros Kapellos, Christin S Kuo, Ludvig Larsson, Michael A. Leney-Greene, Kyungtae Lim, Monika Litviňuková, Ji Lu, Leif S. Ludwig, Wendy Luo, Henrike Maatz, Elo Madissoon, Lira Mamanova, Kasidet Manakongtreecheep, Charles-Hugo Marquette, Ian Mbano, Alexi Marie McAdams, Ross J Metzger, Ahmad N. Nabhan, Sarah K. Nyquist, Lolita Penland, Olivier B. Poirion, Sergio Poli, CanCan Qi, Rachel Queen, Daniel Reichart, Ivan Rosas, Jonas Schupp, Rahul Sinha, Rene V Sit, Dorothee Diogo, Michal Slyper, Neal Smith, Alex Sountoulidis, Maximilian Strunz, Dawei Sun, Carlos Talavera-López, Peng Tan, Jessica Tantivit, Kyle J. Travaglini, Nathan R Tucker, Katherine Vernon, Marc H Wadsworth, Julia Waldman, Xiuting Wang, Wenjun Yan, William Zhao, Carly G. K. Ziegler, The NHLBI LungMAP Consortium, The Human Cell Atlas Lung Biological Network
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis. ### Competing Interest Statement N.K. was a consultant to Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, Optikira and received non-financial support from MiRagen. All of these outside the work reported. J.L. is a scientific consultant for 10X Genomics Inc A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Asimov, and Neogene Therapeutics O.R.R., is a co-inventor on patent applications filed by the Broad Institute to inventions relating to single cell genomics applications, such as in PCT/US2018/060860 and US Provisional Application No. 62/745,259. A.K.S. compensation for consulting and SAB membership from Honeycomb Biotechnologies, Cellarity, Cogen Therapeutics, Orche Bio, and Dahlia Biosciences. S.A.T. was a consultant at Genentech, Biogen and Roche in the last three years. F.J.T. reports receiving consulting fees from Roche Diagnostics GmbH, and ownership interest in Cellarity Inc. L.V. is funder of Definigen and Bilitech two biotech companies using hPSCs and organoid for disease modelling and cell based therapy.
18,458 downloads bioRxiv bioinformatics
Over the past 75 years, a number of statisticians have advised that the data-analysis method known as null-hypothesis significance testing (NHST) should be deprecated (Berkson, 1942; Halsey et al., 2015; Wasserstein et al., 2019). The limitations of NHST have been extensively discussed, with a broad consensus that current statistical practice in the biological sciences needs reform. However, there is less agreement on reform’s specific nature, with vigorous debate surrounding what would constitute a suitable alternative (Altman et al., 2000; Benjamin et al., 2017; Cumming and Calin-Jageman, 2016). An emerging view is that a more complete analytic technique would use statistical graphics to estimate effect sizes and evaluate their uncertainty (Cohen, 1994; Cumming and Calin-Jageman, 2016). As these estimation methods require only minimal statistical retraining, they have great potential to shift the current data-analysis culture away from dichotomous thinking towards quantitative reasoning (Claridge-Chang and Assam, 2016). The evolution of statistics has been inextricably linked to the development of quantitative displays that support complex visual reasoning (Tufte, 2001). We consider that the graphic we describe here as estimation plot is the most intuitive way to display the complete statistical information about experimental data sets. However, a major obstacle to adopting estimation plots is accessibility to suitable software. To lower this hurdle, we have developed free software that makes high-quality estimation plotting available to all. Here, we explain the rationale for estimation plots by contrasting them with conventional charts used to display data with NHST results, and describe how the use of these graphs affords five major analytical advantages.
18,226 downloads bioRxiv bioinformatics
Accurate prediction of protein structure is one of the central challenges of biochemistry. Despite significant progress made by co-evolution methods to predict protein structure from signatures of residue-residue coupling found in the evolutionary record, a direct and explicit mapping between protein sequence and structure remains elusive, with no substantial recent progress. Meanwhile, rapid developments in deep learning, which have found remarkable success in computer vision, natural language processing, and quantum chemistry raise the question of whether a deep learning based approach to protein structure could yield similar advancements. A key ingredient of the success of deep learning is the reformulation of complex, human-designed, multi-stage pipelines with differentiable models that can be jointly optimized end-to-end. We report the development of such a model, which reformulates the entire structure prediction pipeline using differentiable primitives. Achieving this required combining four technical ideas: (1) the adoption of a recurrent neural architecture to encode the internal representation of protein sequence, (2) the parameterization of (local) protein structure by torsional angles, which provides a way to reason over protein conformations without violating the covalent chemistry of protein chains, (3) the coupling of local protein structure to its global representation via recurrent geometric units, and (4) the use of a differentiable loss function to capture deviations between predicted and experimental structures. To our knowledge this is the first end-to-end differentiable model for learning of protein structure. We test the effectiveness of this approach using two challenging tasks: the prediction of novel protein folds without the use of co-evolutionary information, and the prediction of known protein folds without the use of structural templates. On the first task the model achieves state-of-the-art performance, even when compared to methods that rely on co-evolutionary data. On the second task the model is competitive with methods that use experimental protein structures as templates, achieving 3-7Å accuracy despite being template-free. Beyond protein structure prediction, end-to-end differentiable models of proteins represent a new paradigm for learning and modeling protein structure, with potential applications in docking, molecular dynamics, and protein design.
18,098 downloads bioRxiv bioinformatics
Martin Weigert, Deborah Schmidt, Tobias Boothe, Andreas Müller, Alexandr Dibrov, Akanskha Jain, Benjamin Wilhelm, Coleman Broaddus, Siân Culley, Mauricio Rocha-Martins, Fabián Segovia-Miranda, Caren Norden, Ricardo D Henriques, M Zerial, Michele Solimena, Jochen Christian Rink, Pavel Tomancak, Loïc A Royer, Florian Jug, Eugene W Myers
Fluorescence microscopy is a key driver of discoveries in the life-sciences, with observable phenomena being limited by the optics of the microscope, the chemistry of the fluorophores, and the maximum photon exposure tolerated by the sample. These limits necessitate trade-offs between imaging speed, spatial resolution, light exposure, and imaging depth. In this work we show how image restoration based on deep learning extends the range of biological phenomena observable by microscopy. On seven concrete examples we demonstrate how microscopy images can be restored even if 60-fold fewer photons are used during acquisition, how near isotropic resolution can be achieved with up to 10-fold under-sampling along the axial direction, and how tubular and granular structures smaller than the diffraction limit can be resolved at 20-times higher frame-rates compared to state-of-the-art methods. All developed image restoration methods are freely available as open source software in Python, FIJI, and KNIME.
17,850 downloads bioRxiv bioinformatics
Uniform Manifold Approximation and Projection (UMAP) is a recently-published non-linear dimensionality reduction technique. Another such algorithm, t-SNE, has been the default method for such task in the past years. Herein we comment on the usefulness of UMAP high-dimensional cytometry and single-cell RNA sequencing, notably highlighting faster runtime and consistency, meaningful organization of cell clusters and preservation of continuums in UMAP compared to t-SNE.
16,828 downloads bioRxiv bioinformatics
Kevin R Moon, David van Dijk, Zheng Wang, Scott Gigante, Daniel B Burkhardt, William S. Chen, Kristina Yim, Antonia van den Elzen, Matthew J Hirn, Ronald R. Coifman, Natalia B Ivanova, Guy Wolf, Smita Krishnaswamy
With the advent of high-throughput technologies measuring high-dimensional biological data, there is a pressing need for visualization tools that reveal the structure and emergent patterns of data in an intuitive form. We present PHATE, a visualization method that captures both local and global nonlinear structure in data by an information-geometric distance between datapoints. We perform extensive comparison between PHATE and other tools on a variety of artificial and biological datasets, and find that it consistently preserves a range of patterns in data including continual progressions, branches, and clusters. We define a manifold preservation metric DEMaP to show that PHATE produces quantitatively better denoised embeddings than existing visualization methods. We show that PHATE is able to gain unique insight from a newly generated scRNA-seq dataset of human germ layer differentiation. Here, PHATE reveals a dynamic picture of the main developmental branches in unparalleled detail, including the identification of three novel subpopulations. Finally, we show that PHATE is applicable to a wide variety of datatypes including mass cytometry, single-cell RNA-sequencing, Hi-C, and gut microbiome data, where it can generate interpretable insights into the underlying systems.
16,466 downloads bioRxiv bioinformatics
Using single-cell -omics data, it is now possible to computationally order cells along trajectories, allowing the unbiased study of cellular dynamic processes. Since 2014, more than 50 trajectory inference methods have been developed, each with its own set of methodological characteristics. As a result, choosing a method to infer trajectories is often challenging, since a comprehensive assessment of the performance and robustness of each method is still lacking. In order to facilitate the comparison of the results of these methods to each other and to a gold standard, we developed a global framework to benchmark trajectory inference tools. Using this framework, we compared the trajectories from a total of 29 trajectory inference methods, on a large collection of real and synthetic datasets. We evaluate methods using several metrics, including accuracy of the inferred ordering, correctness of the network topology, code quality and user friendliness. We found that some methods, including Slingshot, TSCAN and Monocle DDRTree, clearly outperform other methods, although their performance depended on the type of trajectory present in the data. Based on our benchmarking results, we therefore developed a set of guidelines for method users. However, our analysis also indicated that there is still a lot of room for improvement, especially for methods detecting complex trajectory topologies. Our evaluation pipeline can therefore be used to spearhead the development of new scalable and more accurate methods, and is available at github.com/dynverse/dynverse. To our knowledge, this is the first comprehensive assessment of trajectory inference methods. For now, we exclusively evaluated the methods on their default parameters, but plan to add a detailed parameter tuning procedure in the future. We gladly welcome any discussion and feedback on key decisions made as part of this study, including the metrics used in the benchmark, the quality control checklist, and the implementation of the method wrappers. These discussions can be held at github.com/dynverse/dynverse/issues.
15,516 downloads bioRxiv bioinformatics
To extract patterns from neuroimaging data, various statistical methods and machine learning algorithms have been explored for the diagnosis of Alzheimer′s disease among older adults in both clinical and research applications; however, distinguishing between Alzheimer′s and healthy brain data has been challenging in older adults (age > 75) due to highly similar patterns of brain atrophy and image intensities. Recently, cutting-edge deep learning technologies have rapidly expanded into numerous fields, including medical image analysis. This paper outlines state-of-the-art deep learning-based pipelines employed to distinguish Alzheimer′s magnetic resonance imaging (MRI) and functional MRI (fMRI) from normal healthy control data for a given age group. Using these pipelines, which were executed on a GPU-based high-performance computing platform, the data were strictly and carefully preprocessed. Next, scale- and shift-invariant low- to high-level features were obtained from a high volume of training images using convolutional neural network (CNN) architecture. In this study, fMRI data were used for the first time in deep learning applications for the purposes of medical image analysis and Alzheimer′s disease prediction. These proposed and implemented pipelines, which demonstrate a significant improvement in classification output over other studies, resulted in high and reproducible accuracy rates of 99.9% and 98.84% for the fMRI and MRI pipelines, respectively. Additionally, for clinical purposes, subject-level classification was performed, resulting in an average accuracy rate of 94.32% and 97.88% for the fMRI and MRI pipelines, respectively. Finally, a decision making algorithm designed for the subject-level classification improved the rate to 97.77% for fMRI and 100% for MRI pipelines.
14,955 downloads bioRxiv bioinformatics
Starting from December 2019, a novel coronavirus, later named 2019-nCoV, was found to cause severe and rapid pandemic in China. Basing on the structural information, we have predicted a list of commercial medicines which may function as inhibitors for 2019-nCoV by targeting its main protease Mpro. These drugs may also be effective for other coronaviruses with similar Mpro binding sites and pocket structures.
14,689 downloads bioRxiv bioinformatics
Motivation: The alignment of sequencing reads to a transcriptome is a common and important step in many RNA-seq analysis tasks. When aligning RNA-seq reads directly to a transcriptome (as is common in the de novo setting or when a trusted reference annotation is available), care must be taken to report the potentially large number of multi-mapping locations per read. This can pose a substantial computational burden for existing aligners, and can considerably slow downstream analysis. Results: We introduce a novel concept, quasi-mapping, and an efficient algorithm implementing this approach for mapping sequencing reads to a transcriptome. By attempting only to report the potential loci of origin of a sequencing read, and not the base-to-base alignment by which it derives from the reference, RapMap --- our tool implementing quasi-mapping --- is capable of mapping sequencing reads to a target transcriptome substantially faster than existing alignment tools. The algorithm we employ to implement quasi-mapping uses several efficient data structures and takes advantage of the special structure of shared sequence prevalent in transcriptomes to rapidly provide highly-accurate mapping information. We demonstrate how quasi-mapping can be successfully applied to the problems of transcript-level quantification from RNA-seq reads and the clustering of contigs from de novo assembled transcriptomes into biologically-meaningful groups. Availability: RapMap is implemented in C++11 and is available as open-source software, under GPL v3, at https://github.com/COMBINE-lab/RapMap.
14,379 downloads bioRxiv bioinformatics
Single-cell RNA-sequencing is fast becoming a major technology that is revolutionizing biological discovery in fields such as development, immunology and cancer. The ability to simultaneously measure thousands of genes at single cell resolution allows, among other prospects, for the possibility of learning gene regulatory networks at large scales. However, scRNA-seq technologies suffer from many sources of significant technical noise, the most prominent of which is dropout due to inefficient mRNA capture. This results in data that has a high degree of sparsity, with typically only 10% non-zero values. To address this, we developed MAGIC (Markov Affinity-based Graph Imputation of Cells), a method for imputing missing values, and restoring the structure of the data. After MAGIC, we find that two- and three-dimensional gene interactions are restored and that MAGIC is able to impute complex and non-linear shapes of interactions. MAGIC also retains cluster structure, enhances cluster-specific gene interactions and restores trajectories, as demonstrated in mouse retinal bipolar cells, hematopoiesis, and our newly generated epithelial-to-mesenchymal transition dataset.
14,131 downloads bioRxiv bioinformatics
We have built a statistical package called Ballgown for estimating differential expression of genes, transcripts, or exons from RNA sequencing experiments. Ballgown is designed to work with the popular Cufflinks transcript assembly software and uses well-motivated statistical methods to provide estimates of changes in expression. It permits statistical analysis at the transcript level for a wide variety of experimental designs, allows adjustment for confounders, and handles studies with continuous covariates. Ballgown provides improved statistical significance estimates as compared to the Cuffdiff differential expression tool included with Cufflinks. We demonstrate the flexibility of the Ballgown package by re-analyzing 667 samples from the GEUVADIS study to identify transcript-level eQTLs and identify non-linear artifacts in transcript data. Our package is freely available from: https://github.com/alyssafrazee/ballgown
13,696 downloads bioRxiv bioinformatics
Ancestry deconvolution, the task of identifying the ancestral origin of chromosomal segments in admixed individuals, has important implications, from mapping disease genes to identifying candidate loci under natural selection. To date, however, most existing methods for ancestry deconvolution are typically limited to two or three ancestral populations, and cannot resolve contributions from populations related at a sub-continental scale. We describe Ancestry Composition, a modular three-stage pipeline that efficiently and accurately identifies the ancestral origin of chromosomal segments in admixed individuals. It assumes the genotype data have been phased. In the first stage, a support vector machine classifier assigns tentative ancestry labels to short local phased genomic regions. In the second stage, an autoregressive pair hidden Markov model simultaneously corrects phasing errors and produces reconciled local ancestry estimates and confidence scores based on the tentative ancestry labels. In the third stage, confidence estimates are recalibrated using isotonic regression. We compiled a reference panel of almost 10,000 individuals of homogeneous ancestry, derived from a combination of several publicly available datasets and over 8,000 individuals reporting four grandparents with the same country-of-origin from the member database of the personal genetics company, 23andMe, Inc., and excluding outliers identified through principal components analysis (PCA). In cross-validation experiments, Ancestry Composition achieves high precision and recall for labeling chromosomal segments across over 25 different populations worldwide.
13,019 downloads bioRxiv bioinformatics
Background: Data sharing accelerates scientific progress but sharing individual level data while preserving patient privacy presents a barrier. Methods and Results: Using pairs of deep neural networks, we generated simulated, synthetic "participants" that closely resemble participants of the SPRINT trial. We showed that such paired networks can be trained with differential privacy, a formal privacy framework that limits the likelihood that queries of the synthetic participants' data could identify a real a participant in the trial. Machine-learning predictors built on the synthetic population generalize to the original dataset. This finding suggests that the synthetic data can be shared with others, enabling them to perform hypothesis-generating analyses as though they had the original trial data. Conclusions: Deep neural networks that generate synthetic participants facilitate secondary analyses and reproducible investigation of clinical datasets by enhancing data sharing while preserving participant privacy.
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