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Biomedical subjects

Gene H Golub

Publications and source records attributed to Gene H Golub.

3 recordsLinked to original sources

Integrative analysis of genome-scale data by using pseudoinverse projection predicts novel correlation between DNA replication and RNA transcription.

We describe an integrative data-driven mathematical framework that formulates any number of genome-scale molecular biological data sets in terms of one chosen set of data samples, or of profiles extracted mathematically from data samples, designated the "basis" set. By using pseudoinverse projection, the molecular biological profiles of the data samples are least-squares-approximated as superpositions of the basis profiles. Reconstruction of the data in the basis simulates experimental observation of only the cellular states manifest in the data that correspond to those of the basis. Classification of the data samples according to their reconstruction in the basis, rather than their overall measured profiles, maps the cellular states of the data onto those of the basis and gives a global picture of the correlations and possibly also causal coordination of these two sets of states. We illustrate this framework with an integration of yeast genome-scale proteins' DNA-binding data with cell cycle mRNA expression time course data. Novel correlation between DNA replication initiation and RNA transcription during the yeast cell cycle, which might be due to a previously unknown mechanism of regulation, is predicted.

Cell Cycle↗

Missing value estimation for DNA microarray gene expression data: local least squares imputation.

MOTIVATION: Gene expression data often contain missing expression values. Effective missing value estimation methods are needed since many algorithms for gene expression data analysis require a complete matrix of gene array values. In this paper, imputation methods based on the least squares formulation are proposed to estimate missing values in the gene expression data, which exploit local similarity structures in the data as well as least squares optimization process. RESULTS: The proposed local least squares imputation method (LLSimpute) represents a target gene that has missing values as a linear combination of similar genes. The similar genes are chosen by k-nearest neighbors or k coherent genes that have large absolute values of Pearson correlation coefficients. Non-parametric missing values estimation method of LLSimpute are designed by introducing an automatic k-value estimator. In our experiments, the proposed LLSimpute method shows competitive results when compared with other imputation methods for missing value estimation on various datasets and percentages of missing values in the data. AVAILABILITY: The software is available at http://www.cs.umn.edu/~hskim/tools.html CONTACT: hpark@cs.umn.edu

Algorithms↗

Simultaneous registration and activation detection for fMRI.

Registration using the least-squares cost function is sensitive to the intensity fluctuations caused by the blood oxygen level dependent (BOLD) signal in functional MRI (fMRI) experiments, resulting in stimulus-correlated motion errors. These errors are severe enough to cause false-positive clusters in the activation maps of datasets acquired from 3T scanners. This paper presents a new approach to resolving the coupling between registration and activation. Instead of treating the two problems as individual steps in a sequence, they are combined into a single least-squares problem and are solved simultaneously. Robustness tests on a variety of simulated three-dimensional EPI datasets show that the stimulus-correlated motion errors are removed, resulting in a substantial decrease in false-positive and false-negative activation rates. The new method is also shown to decorrelate the motion estimates from the stimulus by testing it on different in vivo fMRI datasets acquired from two different 3T scanners.

Algorithms↗