Biomedical subjects

Alexander Gordon

Publications and source records attributed to Alexander Gordon.

5 recordsLinked to original sources

PubMed2006

Assessing stability of gene selection in microarray data analysis.

BACKGROUND: The number of genes declared differentially expressed is a random variable and its variability can be assessed by resampling techniques. Another important stability indicator is the frequency with which a given gene is selected across subsamples. We have conducted studies to assess stability and some other properties of several gene selection procedures with biological and simulated data. RESULTS: Using resampling techniques we have found that some genes are selected much less frequently (across sub-samples) than other genes with the same adjusted p-values. The extent to which this type of instability manifests itself can be assessed by a method introduced in this paper. The effect of correlation between gene expression levels on the performance of multiple testing procedures is studied by computer simulations. CONCLUSION: Resampling represents a tool for reducing the set of initially selected genes to those with a sufficiently high selection frequency. Using resampling techniques it is also possible to assess variability of different performance indicators. Stability properties of several multiple testing procedures are described at length in the present paper.

Biomarkers, Tumor↗

PubMed2005

The choice of optimal distance measure in genome-wide datasets.

MOTIVATION: Many types of genomic data are naturally represented as binary vectors. Numerous tasks in computational biology can be cast as analysis of relationships between these vectors, and the first step is, frequently, to compute their pairwise distance matrix. Many distance measures have been proposed in the literature, but there is no theory justifying the choice of distance measure. RESULTS: We examine the approaches to measuring distances between binary vectors and study the characteristic properties of various distance measures and their performance in several tasks of genome analysis. Most distance measures between binary vectors turn out to belong to a single parametric family, namely generalized average-based distance with different exponents. We show that descriptive statistics of distance distribution, such as skewness and kurtosis, can guide the appropriate choice of the exponent. On the contrary, the more familiar distance properties, such as metric and additivity, appear to have much less effect on the performance of distances. AVAILABILITY: R code GADIST and Supplementary material are available at http://research.stowers-institute.org/bioinfo/

Algorithms↗

PubMed2005

Leg length inequality in total hip arthroplasty.

Postoperative leg length inequality after total hip arthroplasty frequently leads to medical liability issues because no standard exists regarding the acceptable disparity. Modular stems allow control of offset, independent sizing of the distal femoral anatomy, as well as proximal medullary sizing. The authors compared the restoration of leg length in two cohort protocols. In the 2001 cohort, tapered stems were exclusively used, giving priority to fit and fill of the medullary canal. In the 2004 cohort, porous-tapered stems, or an S-ROM modular stem (DePuy Orthopaedics Inc., Warsaw, Ind) when needed, were used based on preoperative templating to restore the center of femoral head rotation. Prior to and after surgery, length from center measurements were taken (center of rotation of the femoral head to the top of the lesser trochanter) and the vertical vector to compare the difference in actual leg length. In the 2001 cohort, the mean increase of length from center was 9 mm (7 mm leg length). In the 2004 cohort, 25% of the hips were inappropriate for tapered stems. S-ROMs were used because a tapered stem would lengthen the leg. In the standard offset tapered stem, the mean increase of length from center was 6 mm (4 mm leg length). In the high offset tapered stem, the mean increase of length from center was 7 mm (5 mm leg length). In the S-ROM stem with varying offsets, the mean increase of length from center was 6 mm (4 mm leg length). Only the S-ROM consistently avoids overlengthening in the majority of patients.

Arthroplasty, Replacement, Hip↗

PubMed2004

Multivariate search for differentially expressed gene combinations.

BACKGROUND: To identify differentially expressed genes, it is standard practice to test a two-sample hypothesis for each gene with a proper adjustment for multiple testing. Such tests are essentially univariate and disregard the multidimensional structure of microarray data. A more general two-sample hypothesis is formulated in terms of the joint distribution of any sub-vector of expression signals. RESULTS: By building on an earlier proposed multivariate test statistic, we propose a new algorithm for identifying differentially expressed gene combinations. The algorithm includes an improved random search procedure designed to generate candidate gene combinations of a given size. Cross-validation is used to provide replication stability of the search procedure. A permutation two-sample test is used for significance testing. We design a multiple testing procedure to control the family-wise error rate (FWER) when selecting significant combinations of genes that result from a successive selection procedure. A target set of genes is composed of all significant combinations selected via random search. CONCLUSIONS: A new algorithm has been developed to identify differentially expressed gene combinations. The performance of the proposed search-and-testing procedure has been evaluated by computer simulations and analysis of replicated Affymetrix gene array data on age-related changes in gene expression in the inner ear of CBA mice.

Aging↗

PubMedDate not supplied

Management of supracondylar fractures of humerus with condylar involvement in children.

The intent of this study was to heighten awareness and to present the authors' experience of an uncommon supracondylar humerus fracture in children. Twenty-two children were studied over a period of 18 years. The average age was 7 years, and oldest child was 11 years at time of injury. The fracture subtypes with medial condyle, lateral condyle, and intercondylar extensions were classified based on radiographs. The patients were followed for an average of 6.5 years. Eighteen injuries (82%) were graded excellent or good, and there were two each with fair or poor outcomes. The most common complication was loss of carrying angle of more than 10 degrees, which occurred in three children. The best results were seen in cases where three or four cross-fixing wires were used across the fractures. The authors recommend closed reduction techniques and percutaneous multiple cross-pin fixation for the displaced fracture. The fracture is unique and distinctive enough to warrant a designation as supracondylar fracture type IV with subtypes in the younger child.

Bone Wires↗