The goals of the MELANIE project are to determine if disease-associated patterns can be detected in high resolution two-dimensional polyacrylamide gel electrophoresis (HR 2D-PAGE) images and if a diagnosis can be established automatically by computer. The ELSIE/MELANIE system is a set of computer programs which automatically detect, quantify, and compare protein spots shown on HR 2D-PAGE images. Classification programs help the physician to find disease-associated patterns from a given set of two-dimensional gel electrophoresis images and to form diagnostic rules. Prototype expert systems that use these rules to establish a diagnosis from new HR 2D-PAGE images have been developed. They successfully diagnosed cirrhosis of the liver and were able to distinguish a variety of cancer types from biopsies known to be cancerous.

The interpretation of two-dimensional gel electrophoresis (2-DGE) profiles can be facilitated by artificial intelligence and machine learning programs. We have incorporated into our 2-DGE computer analysis system (termed MELANIE-Medical Electrophoresis Analysis Interactive Expert system) a program which automatically classifies 2-DGE patterns using heuristic clustering analysis. This program is a step toward machine learning. In this publication, we describe the classification method and the preliminary results obtained with liver biopsy electrophoretograms. Heuristic clustering is also compared to other classification techniques.

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Isoelectric focusing in mixed carrier ampholyte‐immobilized pH gradients (CA‐IPG) is an effective way to separate proteins by charge. A method to prepare CA‐IPG in capillary tubes and the description of the equipment used are outlined. Two‐dimensional gel electrophoresis patterns of human serum and liver biopsies, with isoelectric focusing and CA‐IPG as the first dimension, are presented. The comparison with two‐dimensional gel electrophoresis patterns obtained by conventional carrier ampholyte pH gradient separation shows the excellent resolution and potential of this technique.

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