Dataset Information

An improved and explicit surrogate variable analysis procedure by coefficient adjustment.

ABSTRACT: Unobserved environmental, demographic and technical factors canadversely affect the estimation and testing of the effects ofprimary variables. Surrogate variable analysis, proposed to tacklethis problem, has been widely used in genomic studies. To estimatehidden factors that are correlated with the primary variables,surrogate variable analysis performs principal component analysiseither on a subset of features or on all features, but weightingeach differently. However, existing approaches may fail to identifyhidden factors that are strongly correlated with the primaryvariables, and the extra step of feature selection and weightcalculation makes the theoretical investigation of surrogatevariable analysis challenging. In this paper, we propose an improvedsurrogate variable analysis, using all measured features, that has anatural connection with restricted least squares, which allows us tostudy its theoretical properties. Simulation studies and real-dataanalysis show that the method is competitive with state-of-the-artmethods.

SUBMITTER: Lee S

PROVIDER: S-EPMC5627626 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An improved and explicit surrogate variable analysis procedure by coefficient adjustment.

Lee Seunggeun S Sun Wei W Wright Fred A FA Zou Fei F

Biometrika 20170421 2

Unobserved environmental, demographic and technical factors canadversely affect the estimation and testing of the effects ofprimary variables. Surrogate variable analysis, proposed to tacklethis problem, has been widely used in genomic studies. To estimatehidden factors that are correlated with the primary variables,surrogate variable analysis performs principal component analysiseither on a subset of features or on all features, but weightingeach differently. However, existing approaches may fa ...[more]

PMID: 29430031

Similar Datasets

Project description:BackgroundDirected acyclic graphs (DAGs) are an effective means of presenting expert-knowledge assumptions when selecting adjustment variables in epidemiology, whereas the change-in-estimate procedure is a common statistics-based approach. As DAGs imply specific empirical relationships which can be explored by the change-in-estimate procedure, it should be possible to combine the two approaches. This paper proposes such an approach which aims to produce well-adjusted estimates for a given research question, based on plausible DAGs consistent with the data at hand, combining prior knowledge and standard regression methods.MethodsBased on the relationships laid out in a DAG, researchers can predict how a collapsible estimator (e.g. risk ratio or risk difference) for an effect of interest should change when adjusted on different variable sets. Implied and observed patterns can then be compared to detect inconsistencies and so guide adjustment-variable selection.ResultsThe proposed approach involves i. drawing up a set of plausible background-knowledge DAGs; ii. starting with one of these DAGs as a working DAG, identifying a minimal variable set, S, sufficient to control for bias on the effect of interest; iii. estimating a collapsible estimator adjusted on S, then adjusted on S plus each variable not in S in turn ("add-one pattern") and then adjusted on the variables in S minus each of these variables in turn ("minus-one pattern"); iv. checking the observed add-one and minus-one patterns against the pattern implied by the working DAG and the other prior DAGs; v. reviewing the DAGs, if needed; and vi. presenting the initial and all final DAGs with estimates.ConclusionThis approach to adjustment-variable selection combines background-knowledge and statistics-based approaches using methods already common in epidemiology and communicates assumptions and uncertainties in a standardized graphical format. It is probably best suited to areas where there is considerable background knowledge about plausible variable relationships. Researchers may use this approach as an additional tool for selecting adjustment variables when analyzing epidemiological data.

Project description:BackgroundGenomic data production is at its highest level and continues to increase, making available novel primary data and existing public data to researchers for exploration. Here we explore the consequences of "batch" correction for biological discovery in two publicly available expression datasets. We consider this to include the estimation of and adjustment for wide-spread systematic heterogeneity in genomic measurements that is unrelated to the effects under study, whether it be technical or biological in nature.MethodsWe present three illustrative data analyses using surrogate variable analysis (SVA) and describe how to perform artifact discovery in light of natural heterogeneity within biological groups, secondary biological questions of interest, and non-linear treatment effects in a dataset profiling differentiating pluripotent cells (GSE32923) and another from human brain tissue (GSE30272).ResultsCareful specification of biological effects of interest is very important to factor-based approaches like SVA. We demonstrate greatly sharpened global and gene-specific differential expression across treatment groups in stem cell systems. Similarly, we demonstrate how to preserve major non-linear effects of age across the lifespan in the brain dataset. However, the gains in precisely defining known effects of interest come at the cost of much other information in the "cleaned" data, including sex, common copy number effects and sample or cell line-specific molecular behavior.ConclusionsOur analyses indicate that data "cleaning" can be an important component of high-throughput genomic data analysis when interrogating explicitly defined effects in the context of data affected by robust technical artifacts. However, caution should be exercised to avoid removing biological signal of interest. It is also important to note that open data exploration is not possible after such supervised "cleaning", because effects beyond those stipulated by the researcher may have been removed. With the goal of making these statistical algorithms more powerful and transparent to researchers in the biological sciences, we provide exploratory plots and accompanying R code for identifying and guiding "cleaning" process (https://github.com/andrewejaffe/StemCellSVA). The impact of these methods is significant enough that we have made newly processed data available for the brain data set at http://braincloud.jhmi.edu/plots/ and GSE30272.

Dataset Information

An improved and explicit surrogate variable analysis procedure by coefficient adjustment.

Publications

An improved and explicit surrogate variable analysis procedure by coefficient adjustment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets