Dual sample melting curve cluster and cost analysis
AssigneeCanon U.S.A., Inc.
InventorsYang Yang, Bradley Scott Denney, Attaullah Seikh
Life of this patent
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Abstract
The present invention relates to methods and systems for the analysis of nucleic acids present in biological samples, and more specifically, relates to clustering melt curves derived from high resolution thermal melt analysis performed on a sample of nucleic acids, the resulting clusters being usable, in one embodiment, for analyzing the sequences of nucleic acids and to classify their genotypes that are useful for determining the identity of the genotype of a nucleic acid that is present in a biological sample.
Claims17
A method for determining cluster centers for curves associated with biological reactions on a device having at least two biological samples, the method comprising:
- providing a device having at least two biological samples;
- providing a thermal system in communication with the device, the thermal system controlling a temperature within the device causing a biological reaction in each of the biological samples, wherein the biological reaction is a thermal melt reaction;
- providing a controller in communication with the device, the controller providing instructions for:
- generating at least one curve indicative of the biological reaction in each of the biological samples, each curve representing a change in a physical parameter associated with the biological sample as a function of the temperature within the device;
- calculating an optimal cluster number for the generated curves;
- building at least one tuple containing cluster centers represented by the curves, wherein the number of cluster centers in each tuple equals the optimal cluster number and each optimal cluster number corresponds to identified tuples;
- for each tuple, calculating a cost value indicative of curves outside of the tuple fitting into clusters associated with the cluster centers in the tuple;
- and
- returning cluster centers in a tuple having a minimum cost value.
A method for determining cluster centers for curves associated with biological reactions on a device, the method comprising:
- providing a device having at least two biological samples;
- providing a thermal system in communication with the device, the thermal system controlling a temperature within the device causing a biological reaction in each of the biological samples, wherein the biological reaction is a thermal melt reaction;
- providing a controller in communication with the device;
- wherein the controller receives data representing at least one curve associated with a biological sample having undergone the biological reaction occurring in the device, each curve representing a change in a physical parameter associated with the biological sample as a function of a temperature within the device;
- wherein the controller provides instructions to:
- calculate an optimal cluster number for the generated at least one curves;
- build at least one tuple containing cluster centers represented by the at least one curves, wherein the number of cluster centers in each tuple equals the optimal cluster number and each optimal cluster number corresponds to identified tuples;
- for each tuple, calculate a cost value indicative of curves outside of the tuple fitting into clusters associated with the cluster centers in the tuple;
- and
- return data representing cluster centers in a tuple having a minimum cost value.
A system for determining cluster centers for curves associated with biological reactions on a device, the system comprising:
- a device having at least two biological samples;
- a thermal system in communication with the device, the thermal system controlling a temperature within the device causing a biological reaction in each of the biological samples, wherein the biological reaction is a thermal melt reaction;
- one or more processors in communication the device;
- a storage medium including instructions, that when executed by the one or more processors:
- generate at least one curve indicative of the biological reaction in each of the biological samples, each curve representing a change in a physical parameter associated with the biological sample as a function of the temperature within the device;
- calculate an optimal cluster number for the generated curves;
- build at least one tuple containing cluster centers represented by the curves, wherein the number of cluster centers in each tuple equals the optimal cluster number and each optimal cluster number corresponds to of identified tuples;
- for each tuple, calculating a cost value indicative of curves outside of the tuple fitting into clusters associated with the cluster centers in the tuple;
- and
- return cluster centers in a tuple having a minimum cost value.
Dependencies are inferred from the claim text.