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Optimal simultaneous superpositioning of multiple structures with missing data.

ABSTRACT: Superpositioning is an essential technique in structural biology that facilitates the comparison and analysis of conformational differences among topologically similar structures. Performing a superposition requires a one-to-one correspondence, or alignment, of the point sets in the different structures. However, in practice, some points are usually 'missing' from several structures, for example, when the alignment contains gaps. Current superposition methods deal with missing data simply by superpositioning a subset of points that are shared among all the structures. This practice is inefficient, as it ignores important data, and it fails to satisfy the common least-squares criterion. In the extreme, disregarding missing positions prohibits the calculation of a superposition altogether.Here, we present a general solution for determining an optimal superposition when some of the data are missing. We use the expectation-maximization algorithm, a classic statistical technique for dealing with incomplete data, to find both maximum-likelihood solutions and the optimal least-squares solution as a special case.The methods presented here are implemented in THESEUS 2.0, a program for superpositioning macromolecular structures. ANSI C source code and selected compiled binaries for various computing platforms are freely available under the GNU open source license from http://www.theseus3d.org.dtheobald@brandeis.eduSupplementary data are available at Bioinformatics online.

SUBMITTER: Theobald DL

PROVIDER: S-EPMC3400950 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Optimal simultaneous superpositioning of multiple structures with missing data.

Theobald Douglas L DL Steindel Phillip A PA

Bioinformatics (Oxford, England) 20120427 15

<h4>Motivation</h4>Superpositioning is an essential technique in structural biology that facilitates the comparison and analysis of conformational differences among topologically similar structures. Performing a superposition requires a one-to-one correspondence, or alignment, of the point sets in the different structures. However, in practice, some points are usually 'missing' from several structures, for example, when the alignment contains gaps. Current superposition methods deal with missing ...[more]

PMID: 22543369

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Project description:In modern scientific research, data are often collected from multiple modalities. Since different modalities could provide complementary information, statistical prediction methods using multi-modality data could deliver better prediction performance than using single modality data. However, one special challenge for using multi-modality data is related to block-missing data. In practice, due to dropouts or the high cost of measures, the observations of a certain modality can be missing completely for some subjects. In this paper, we propose a new DIrect Sparse regression procedure using COvariance from Multi-modality data (DISCOM). Our proposed DISCOM method includes two steps to find the optimal linear prediction of a continuous response variable using block-missing multi-modality predictors. In the first step, rather than deleting or imputing missing data, we make use of all available information to estimate the covariance matrix of the predictors and the cross-covariance vector between the predictors and the response variable. The proposed new estimate of the covariance matrix is a linear combination of the identity matrix, the estimates of the intra-modality covariance matrix and the cross-modality covariance matrix. Flexible estimates for both the sub-Gaussian and heavy-tailed cases are considered. In the second step, based on the estimated covariance matrix and the estimated cross-covariance vector, an extended Lasso-type estimator is used to deliver a sparse estimate of the coefficients in the optimal linear prediction. The number of samples that are effectively used by DISCOM is the minimum number of samples with available observations from two modalities, which can be much larger than the number of samples with complete observations from all modalities. The effectiveness of the proposed method is demonstrated by theoretical studies, simulated examples, and a real application from the Alzheimer's Disease Neuroimaging Initiative. The comparison between DISCOM and some existing methods also indicates the advantages of our proposed method.

Project description:BackgroundIncomplete categorical variables with more than two categories are common in public health data. However, most of the existing missing-data methods do not use the information from nonresponse (missingness) probabilities.MethodsWe propose a nearest-neighbour multiple imputation approach to impute a missing at random categorical outcome and to estimate the proportion of each category. The donor set for imputation is formed by measuring distances between each missing value with other non-missing values. The distance function is calculated based on a predictive score, which is derived from two working models: one fits a multinomial logistic regression for predicting the missing categorical outcome (the outcome model) and the other fits a logistic regression for predicting missingness probabilities (the missingness model). A weighting scheme is used to accommodate contributions from two working models when generating the predictive score. A missing value is imputed by randomly selecting one of the non-missing values with the smallest distances. We conduct a simulation to evaluate the performance of the proposed method and compare it with several alternative methods. A real-data application is also presented.ResultsThe simulation study suggests that the proposed method performs well when missingness probabilities are not extreme under some misspecifications of the working models. However, the calibration estimator, which is also based on two working models, can be highly unstable when missingness probabilities for some observations are extremely high. In this scenario, the proposed method produces more stable and better estimates. In addition, proper weights need to be chosen to balance the contributions from the two working models and achieve optimal results for the proposed method.ConclusionsWe conclude that the proposed multiple imputation method is a reasonable approach to dealing with missing categorical outcome data with more than two levels for assessing the distribution of the outcome. In terms of the choices for the working models, we suggest a multinomial logistic regression for predicting the missing outcome and a binary logistic regression for predicting the missingness probability.

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Optimal simultaneous superpositioning of multiple structures with missing data.

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Optimal simultaneous superpositioning of multiple structures with missing data.

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