Oct 30, 2018

The Markov link method: a nonparametric approach to combine observations from multiple experiments

BioRxiv : the Preprint Server for Biology
Jackson LoperDavid Blei

Abstract

This paper studies measurement linkage. An example from cell biology helps explain the problem: imagine for a given cell we can either sequence the cell's RNA or we can examine its morphology, but not both. Given a cell's morphology, what do we expect to see in its RNA? Given a cell's RNA, what do we expect in its morphology? More broadly, given a measurement of one type, can we predict measurements of the other type? This measurement linkage problem arises in many scientific and technological fields. To solve this problem, we develop a nonparametric approach we dub the "Markov link method" (MLM). The MLM makes a conditional independence assumption that holds in many multi-measurement contexts and provides a a way to estimate the link, the conditional probability of one type of measurement given the other. We derive conditions under which the MLM estimator is consistent and we use simulated data to show that it provides accurate measures of uncertainty. We evaluate the MLM on real data generated by a pair of single-cell RNA sequencing techniques. The MLM characterizes the link between them and helps connect the two notions of cell type derived from each technique. Further, the MLM reveals that some aspects of the link cannot be...Continue Reading

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Mentioned in this Paper

Study
Sequence Determinations, RNA
Science of Morphology
Nucleic Acid Sequencing
Familial Atypical Mole Melanoma Syndrome
Cell Type
Genetic Linkage
CDKN2A wt Allele
RNA
Research Study

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