Ritambhara Singh, Pinar Demetci, Giancarlo Bonora, Vijay Ramani, Choli Lee, He Fang, Zhijun Duan, Xinxian Deng, Jay Shendure, Christine Disteche, William Stafford Noble
{"title":"Unsupervised manifold alignment for single-cell multi-omics data.","authors":"Ritambhara Singh, Pinar Demetci, Giancarlo Bonora, Vijay Ramani, Choli Lee, He Fang, Zhijun Duan, Xinxian Deng, Jay Shendure, Christine Disteche, William Stafford Noble","doi":"10.1145/3388440.3412410","DOIUrl":null,"url":null,"abstract":"<p><p>Integrating single-cell measurements that capture different properties of the genome is vital to extending our understanding of genome biology. This task is challenging due to the lack of a shared axis across datasets obtained from different types of single-cell experiments. For most such datasets, we lack corresponding information among the cells (samples) and the measurements (features). In this scenario, unsupervised algorithms that are capable of aligning single-cell experiments are critical to learning an <i>in silico</i> co-assay that can help draw correspondences among the cells. Maximum mean discrepancy-based manifold alignment (MMD-MA) is such an unsupervised algorithm. Without requiring correspondence information, it can align single-cell datasets from different modalities in a common shared latent space, showing promising results on simulations and a small-scale single-cell experiment with 61 cells. However, it is essential to explore the applicability of this method to larger single-cell experiments with thousands of cells so that it can be of practical interest to the community. In this paper, we apply MMD-MA to two recent datasets that measure transcriptome and chromatin accessibility in ~2000 single cells. To scale the runtime of MMD-MA to a more substantial number of cells, we extend the original implementation to run on GPUs. We also introduce a method to automatically select one of the user-defined parameters, thus reducing the hyperparameter search space. We demonstrate that the proposed extensions allow MMD-MA to accurately align state-of-the-art single-cell experiments.</p>","PeriodicalId":72044,"journal":{"name":"ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1145/3388440.3412410","citationCount":"38","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1145/3388440.3412410","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 38
Abstract
Integrating single-cell measurements that capture different properties of the genome is vital to extending our understanding of genome biology. This task is challenging due to the lack of a shared axis across datasets obtained from different types of single-cell experiments. For most such datasets, we lack corresponding information among the cells (samples) and the measurements (features). In this scenario, unsupervised algorithms that are capable of aligning single-cell experiments are critical to learning an in silico co-assay that can help draw correspondences among the cells. Maximum mean discrepancy-based manifold alignment (MMD-MA) is such an unsupervised algorithm. Without requiring correspondence information, it can align single-cell datasets from different modalities in a common shared latent space, showing promising results on simulations and a small-scale single-cell experiment with 61 cells. However, it is essential to explore the applicability of this method to larger single-cell experiments with thousands of cells so that it can be of practical interest to the community. In this paper, we apply MMD-MA to two recent datasets that measure transcriptome and chromatin accessibility in ~2000 single cells. To scale the runtime of MMD-MA to a more substantial number of cells, we extend the original implementation to run on GPUs. We also introduce a method to automatically select one of the user-defined parameters, thus reducing the hyperparameter search space. We demonstrate that the proposed extensions allow MMD-MA to accurately align state-of-the-art single-cell experiments.