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M M Skolnick

Publications and source records attributed to M M Skolnick.

5 recordsLinked to original sources
PubMed1991

A two-dimensional electrophoresis-related laboratory information processing system: spot matching.

An approach for the computer-assisted analysis of two-dimensional gels has been developed as a part of our laboratory information processing system (LIPS). This approach relies in part on an algorithm for the pairwise matching of protein spots. The matching process initially matches spots based on a cross-correlational measure of how well neighboring spots align. While this first pass correctly determines most spot correspondences and noncorrespondences, it can make errors. Higher accuracy is obtained by monitoring the consistency of spot match decisions in a second pass, which demands that neighboring spot pairs that align spatially must also have been found to match in the first pass. Pairwise comparisons of gels are combined into n-way comparisons by matching spot lists of gels to "master" gel spot lists, which in turn are matched to higher level masters, resulting in a hierarchy of matched spots. After each pairwise match the results are reviewed and corrected with the assistance of a graphical match-editor. Results are given for 19 single-cell-derived lymphoid clones in which the presence of a mutation had previously been established, each processed in duplicate. Only one of 46 spot changes failed to be detected, which demonstrates that the strategy is sensitive and efficient for detecting qualitative spot differences.

Algorithms↗
PubMed1986

An algorithm for comparing two-dimensional electrophoretic gels, with particular reference to the study of mutation.

An algorithm dedicated to the detection of presumed mutational events involving the polypeptides displayed with two-dimensional polyacrylamide gel electrophoresis has been described. Because of the large number of gels necessary in most studies of mutation, the algorithm has been designed to minimize operator intervention in its execution. The basic principle involves a comparison of the graph structures of the gels of a father, mother, and one or more children, searching for protein spots in the child not found in either parent. These so-called "orphan" spots are considered a probable manifestation of mutation only after other possible causes of such an isolated event have been excluded as rigorously as possible. At present, the analysis of gels prepared from a platelet or erythrocyte lysate yields about 2% "false-positive" findings, i.e., results in the incorrect designation of a unique spot in a child. These errors can be disposed of by technician intervention. In an experiment designed to simulate the occurrence of mutational events, the algorithm operated with 70% accuracy. Most of the "errors" ("false negatives") occurred when the position of the simulated mutant polypeptide coincided in whole or part with that of a preexisting polypeptide, resulting in a class of mutation not detectable by the eye either. With correction for this fact, the accuracy was 84%. Possible improvements in the algorithm which would substantially increase accuracy have been discussed at some length, as have some ideas as to how to manage the large body of data resulting from the operation of the algorithm. A murine experiment designed to validate the approach has been outlined.

Blood Proteins↗
PubMed1982

Computer programs for adapting two-dimensional gels to the study of mutation.

We are attempting to adapt the two-dimensional polyacrylamide gel technology to the search for mutations that after the electrophoretic mobility of proteins. These events are expected to have a frequency on the order of 10(-6). To this end, programs that run on the CytocomputerTM are being developed for comparing the pattern of the gel derived from a child's blood sample with those of the gels of corresponding samples from its parents. We anticipate examining thousands of such trios. Programs are described that perform background normalization, noise filtering, spot detection, gel registration, and, finally, compare the father/mother/child gel trios for the presence of unique protein moieties in the child that are consistent with a mutational event.

Adult↗
PubMed1982

An approach to completely automatic comparison of two-dimensional electrophoresis gels.

The problem addressed is that of determining the similarities and differences appearing in a sequence of two-dimensional polyacrylamide gels where we have no a priori knowledge of the intensity and spatial distribution of the protein spots. It is assumed that the gels are not in precise registration. An attempt is being made to develop a completely automatic program for use in genetic studies, which will compare a sequence of three gels run on samples from father, mother, and child. The program constructs a graph by using as nodes those spot cues that exceed a given intensity threshold. The graphs are then compared to determine an initial subset of spots that are common to all three gels. From this subset of common spots the program then determines whether the remaining graph differences are real or result from quantitative variation causing spots to fall below threshold.

Adult↗