Colon cancer biomarkers

Abstract

Systems and methods for enhancing knowledge discovery from data using multiple learning machines in general and multiple support vector machines in particular. Training data for a learning machine is pre-processed in order to add meaning thereto. Multiple support vector machines, each comprising distinct kernels, are trained with the pre-processed training data and are tested with test data that is pre-processed in the same manner. The test outputs from multiple support vector machines are compared in order to determine which of the test outputs if any represents a optimal solution. Selection of one or more kernels may be adjusted and one or more support vector machines may be retrained and retested. Optimal solutions based on distinct input data sets may be combined to form a new input data set to be input into one or more additional support vector machine. The methods, systems and devices of the present invention comprise use of Support Vector Machines for the identification of patterns that are important for medical diagnosis, prognosis and treatment. Such patterns may be found in many different datasets. The present invention also comprises methods and compositions for the treatment and diagnosis of medical conditions.

Description

RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. patent application Ser. Nos. 09 / 303,386; 09 / 303,387; 09 / 303,389; 09 / 305,345; all filed May 1, 1999; and U.S. patent application Ser. No. 09 / 568,301, filed May 9, 2000; and U.S. patent application Ser. No. 09 / 578,011, filed May 24, 2000 and also claims the benefit of U.S. Provisional Patent Application No. 60 / 161,806, filed Oct. 27, 1999; of U.S. Provisional Patent Application No. 60 / 168,703, filed Dec. 2, 1999; of U.S. Provisional Patent Application No. 60 / 184,596, filed Feb. 24, 2000; and of U.S. Provisional Patent Application Ser. No. 60 / 191,219, filed Mar. 22, 2000.TECHNICAL FIELD [0002] The present invention relates to the use of learning machines to identify relevant patterns in biological systems such as genes, gene products, proteins, lipids, and combinations of the same. These patterns in biological systems can be used to diagnose and prognose abnormal physiological states. In addition, the patter...

AI Technical Summary

Benefits of technology

[0024] In a preferred embodiment, the support vector machine is trained using the pre-processed training data set. In this manner, the additional representations of the training data provided by the preprocessing may enhance the learning machine's ability to discover knowledge therefrom. In the particular context of support vector machines, the greater the dimensionality of the training set, the higher the quality of the generalizations that may be derived therefrom. When the knowledge to be discovered from the data relates to a regression or density estimation or where the training output comprises a continuous variable, the training output may be post-processed by optimally categorizing the training output to derive categorizations from the continuous variable.

[0025] A test data set is pre-processed in the same manner as was the training data set. Then, the trained learning machine is tested using the pre-processed test data set. A test output of the trained learning machine may be post-processing to determine if the test output is an optimal solution. Post-processing the test output may comprise interpreting the test output into a format that may be compared with the test data set. Alternative postprocessing steps may enhance the human interpretability or suitability for additional processing of the output data.

[0028] In an exemplary embodiment, a system and method are provided for enhancing knowledge discovery from data using multiple learning machines in general and multiple support vector machines in particular. Training data for a learning machine is pre-processed in order to add meaning thereto. Pre-processing data may involve transforming the data points and / or expanding the data points. By adding meaning to the data, the learning machine is provided with a greater amount of information for processing. With regard to support vector machines in particular, the greater the amount of information that is processed, the better generalizations about the data that may be derived. Multiple support vector machines, each comprising distinct kernels, are trained with the pre-processed training data and are tested with test data that is pre-processed in the same manner. The test outputs from multiple support vector machines are compared in order to determine which of the test outputs if any represents an optimal solution. Selection of one or more kernels may be adjusted and one or more support vector machines may be retrained and retested. When it is determined that an optimal solution has been achieved, live data is pre-processed and input into the support vector machine comprising the kernel that produced the optimal solution. The live output from the learning machine may then be post-processed into a computationally derived alphanumeric classifier for interpretation by a human or computer automated process.

Problems solved by technology

Enormous amounts of data about organisms are being generated in the sequencing of genomes.

In fact, the amount of data being generated by such methods hinders the derivation of useful information.

Problems arise in identifying the thousands of proteins that are found in cells that have been separated on the 2-D gels.

Unfortunately, these methods require multiple steps to analyze a small portion of the proteome.

The current analytical methods are limited in their abilities to manage the large amounts of data generated by these technologies.

Currently, there are no methods, systems or devices for adequately analyzing the data generated by such biological investigations into the genome and proteome.

Recent advancements in database technology have lead to an explosive growth in systems and methods for generating, collecting and storing vast amounts of data.

While database technology enables efficient collection and storage of large data sets, the challenge of facilitating human comprehension of the information in this data is growing ever more difficult.

With many existing techniques the problem has become unapproachable.

The vast amount of data in such a database overwhelms traditional tools for data analysis, such as spreadsheets and ad hoc queries.

Traditional methods of data analysis may be used to create informative reports from data, but do not have the ability to intelligently and automatically assist humans in analyzing and finding patterns of useful knowledge in vast amounts of data.

Likewise, using traditionally accepted reference ranges and standards for interpretation, it is often impossible for humans to identify patterns of useful knowledge even with very small amounts of data.

However, there are various problems with back-propagation neural network approaches that prevent neural networks from being well-controlled learning machines.

For example, a significant drawback of back-propagation neural networks is that the empirical risk function may have many local minimums, a case that can easily obscure the optimal solution from discovery by this technique.

Standard optimization procedures employed by back-propagation neural networks may converge to an answer, but the neural network method cannot guarantee that even a localized minimum is attained much less the desired global minimum.

In particular the skill of the practitioner implementing the neural network determines the ultimate benefit, but even factors as seemingly benign as the random selection of initial weights can lead to poor results.

Furthermore, the convergence of the gradient based method used in neural network learning is inherently slow.

A further drawback is that the sigmoid activation function has a scaling factor, which affects the quality of approximation.

Possibly the largest limiting factor of neural networks as related to knowledge discovery is the “curse of dimensionality” associated with the disproportionate growth in required computational time and power for each additional feature or dimension in the training data.

Within a support vector machine, the dimensionally of the feature space may be huge.

However, the ability of a support vector machine to discover knowledge from a data set is limited in proportion to the information included within the training data set.

Furthermore, the raw output from a support vector machine may not fully disclose the knowledge in the most readily interpretable form.

In addition, the ability of a support vector machine to discover knowledge from data is limited by the selection of a kernel.

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