Method and system for pattern analysis, such as for analyzing oligonucleotide primer extension assay products

• US 6,203,990 B1
• Filed: 04/09/1999
• Issued: 03/20/2001
• Est. Priority Date: 11/06/1998
• Status: Expired due to Fees

• Current Assignee: Mitokor
• Original Assignee: Mitokor
• Inventors: Fahy, Eoin David
• Primary Examiner(s): Brusca, John S.
• Assistant Examiner(s): SIU, STEPHEN C
• Application Number:
  US09/289,793
• Time in Patent Office: 711 Days
• Field of Search: 422/64, 232/30, 435/6, 435/5, 204/612, 204/606
• US Class Current: 435/6.11
• CPC Class Codes: G16B 45/00 ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks

Abstract

A system and corresponding method analyzes data for patterns, such as data produced from DNA sequencers. An ASCII text file, generated by DNA sequencer software, is used as the input source for the pattern analysis software program. This text file contains peak intensity data, identified by gel-lane and mobility, for bands corresponding to 2 sequences of differing length. The software uses gel-mobility values of control DNA samples to identify bands of interest from test samples in the dataset. Spurious data point or artifacts are filtered out in this selection process. The selected data is then imported to a second software program that performs algorithms such as linear progression and curve fitting.

Claims

1. A system for generating information based on biological samples, comprising:

a biological assay device that analyzes a two dimensionally spaced set of biological samples and produces a set of data therefrom, wherein the biological samples include at least one control sample, wherein the set of data includes x-axis and y-axis spatial coordinate values and a quantitative value for each biological sample, and wherein the set of data may include unwanted values; and

a computer having a processor and memory, wherein the computer receives the set of data from the biological assay device, stores the set of data in the memory, and wherein the processor;

determines a two dimensional location of the at least one control sample based on the set of data;

identifies x-axis and y-axis spatial coordinates for the biological samples in the set of data based on the determined two dimensional location of the at least one control sample;

filters the quantitative values of for at least some of the biological samples, from the unwanted values, in the set of data, based on the identified x-axis and y-axis spatial coordinates; and

analyzes the filtered quantitative values of each biological sample, respectively, by comparing the quantitative value of a first portion of the filtered quantitative values of each respective biological sample at a first pair of x-axis and y-axis spatial coordinates with a sum of the quantitative value of the first portion and the quantitative value of a second portion of the filtered quantitative values of each respective biological sample at a second pair of x-axis and y-axis spatial coordinates to produce a displayable report of the analyzed quantitative values.

2. The system of claim 1 wherein the biological assay device includes a DNA sequencer for analyzing an electrophoresis gel having lanes and rows of mitochondrial and extramitochondrial samples, and an as say computer coupled to the DNA sequencer that produces the set of data identifying lanes, scan numbers and intensity values for each sample, wherein at least one predetermined lane includes a plurality of mitochondrial and extramitochondrial control samples, and wherein the processor receives input regarding scan numbers of the mitochondrial and extramitochondrial control samples.

3. The system of claim 1 wherein the biological assay device includes a DNA sequencer for analyzing an electrophoresis gel having lanes and rows of mitochondrial and extramitochondrial samples, and an assay computer coupled to the DNA sequencer that produces the set of data identifying lanes, scan numbers and quantitative values for each sample, and wherein the processor provides a slope correction when filtering the quantitative values.

4. The system of claim 1 wherein the x-axis and y-axis spatial coordinates in the set of data correspond to lanes and scan numbers of an electrophoresis gel, and wherein the processor:

identifies the x-axis and y-axis spatial coordinates for the biological samples in the set of data based on determined lane and scan numbers of the at least one control sample and,

identifies scan numbers for the biological samples that are within a predetermined stringency amount of the scan number of the at least one control sample.

5. The system of claim 1 wherein the biological assay device includes a DNA sequencer for analyzing an electrophoresis gel having lanes and rows of mitochondrial and extramitochondrial samples, and wherein the processor determines a percent mitochondrial load of the biological samples based on the filtered quantitative values.

6. The system of claim 1 wherein the computer includes a network interface, and wherein the computer is coupled to the biological assay device through the network interface.

8. The system of claim 1 wherein the computer includes a spreadsheet application, and wherein the processor executes at least one macro for the spreadsheet application that performs the identifying x-axis and y-axis values and the filtering of the quantitative values.

9. The system of claim 1 wherein the processor provides slope correction and stringency adjustments for filtering the quantitative values.

7. The system of claim wherein the computer includes a web browser, and wherein the displayable report is provided to the web browser for transmission over the Internet.

10. A method for generating information based on biological samples, comprising:

receiving a set of data produced from testing a set of biological samples, wherein the biological samples include test samples and at least one control sample related to at least some of the test samples by space, time or frequency, wherein the set of data includes first and second values and a quantitative value for each test sample;

identifying first or second values corresponding to the control sample in the set of data;

identifying first or second values for at least some of the test samples in the set of data based on the identified first or second values of the control sample and the spatial, temporal or frequency relationship between the control sample and the at least some of the test samples;

filtering the quantitative values for the at least some of the test samples in the set of data based on the identified first or second values; and

analyzing the filtered quantitative values of a selected test sample by comparing the quantitative value of a first portion of the filtered quantitative values of the selected test sample at a first pair of x-axis and y-axis spatial coordinates with a sum of the quantitative value of the first portion and the quantitative value of a second portion of the filtered quantitative values of the selected test sample at a second pair of x-axis and y-axis spatial coordinates.

11. The method of claim 10 wherein the first and second values in the set of data identify lanes and row numbers, respectively, for spatially distinguishing mitochondrial and extramitochondrial test samples, wherein the quantitative values include intensity values for test samples, wherein at least one predetermined lane includes a plurality of mitochondrial and extramitochondrial control samples, and wherein identifying first or second values corresponding to the control sample includes receiving input regarding row numbers of the mitochondrial and extramitochondrial control samples for the set of data, and wherein identifying first or second values for at least some of the test samples includes identifying row numbers based on a preselected lane number for the mitochondrial and extramitochondrial test samples.

12. The method of claim 10 wherein receiving includes receiving the set of data from a DNA sequencer that analyzes an electrophoresis gel having lanes and rows of mitochondrial and extramitochondrial samples, and wherein the first, second and quantitative values in the set of data correspond respectively to lanes, scan numbers and intensity values for each test sample.

13. The method of claim 10 wherein the first and second values correspond respectively to lanes and scan numbers of an electrophoresis gel.

14. The method of claim 10 wherein the first and second values correspond respectively to x-axis and y-axis spatial coordinates.

15. The method of claim 10 wherein analyzing the filtered quantitative values includes determining a percent mitochondrial load of the biological samples based on the filtered quantitative values.

16. The method of claim 10 wherein the first and second values correspond respectively to lanes and scan numbers of an electrophoresis gel, and wherein the method includes providing a slope correction when filtering the quantitative values.

17. The method of claim 10 wherein the first and second values in the set of data correspond to lanes and scan numbers of an electrophoresis gel, and wherein the method includes:

identifying a lane for the test samples in the set of data based on determined lane and scan numbers of the control sample; and

, identifying scan numbers for the test samples that are within a predetermined stringency amount of the scan number of the control sample.

18. The method of claim 10 wherein the first and second values in the set of data correspond respectively to x-axis and y-axis spatial coordinates and wherein identifying first or second values for at least some of the test samples in the set of data identifies x- or y-axis coordinates for the test samples that are within a predetermined stringency amount of x- or y-axis coordinates of the control sample.

19. A computer-readable medium for storing computer readable instructions, the instructions being capable of programming a computer to perform a method, the method comprising:

receiving a set of data produced from testing a set of biological samples, wherein the biological samples include test samples and at least one control sample related to at least some of the test samples by space, time or frequency, wherein the set of data includes first and second values and a quantitative value for each test sample;

identifying first or second values corresponding to the control sample in the set of data;

identifying first or second values for at least some of the test samples in the set of data based on the identified first or second values of the control sample and the spatial, temporal or frequency relationship between the control sample and the at least some of the test samples;

filtering the quantitative values for the at least some of the test samples in the set of data based on the identified first or second values; and

analyzing the filtered quantitative values of a selected one of the test samples by comparing the quantitative value of a first portion of the filtered quantitative values of the selected test sample at a first pair of x-axis and y-axis spatial coordinates with a sum of the quantitative value of the first portion and the quantitative value of a second portion of the filtered quantitative values of the selected test sample at a second pair of x-axis and y-axis spatial coordinates.

20. The computer-readable medium of claim 19 wherein the first and second values in the set of data identify lanes and row numbers, respectively, for spatially distinguishing mitochondrial and extramitochondrial test samples in an electrophoresis gel, wherein the quantitative values include intensity values for test samples, wherein at least one predetermined lane includes a plurality of mitochondrial and extramitochondrial control samples, and wherein identifying first or second values corresponding to the control sample includes receiving input regarding row numbers of the mitochondrial and extramitochondrial control samples for the set of data, and wherein identifying first or second values for at least some of the test samples includes identifying row numbers based on a preselected lane number for the mitochondrial and extramitochondrial test samples.

21. The computer-readable medium of claim 19 wherein receiving includes receiving the set of data from a DNA sequencer that analyzes an electrophoresis gel having lanes and rows of mitochondrial and extramitochondrial samples, and wherein the first, second and quantitative values in the set of data correspond respectively to lanes, scan numbers and intensity values for each test sample.

22. The computer-readable medium of claim 19 wherein the first and second values correspond respectively to lanes and scan numbers of an electrophoresis gel.

23. The computer-readable medium of claim 19 wherein the first and second values correspond respectively to x-axis and y-axis spatial coordinates.

24. The computer-readable medium of claim 19 wherein analyzing the filtered quantitative values includes determining a percent mitochondrial load of the biological samples based on the filtered quantitative values.

25. The computer-readable medium of claim 19 wherein the first and second values correspond respectively to lanes and scan numbers of an electrophoresis gel, and wherein the method includes providing a slope correction when filtering the quantitative values.

26. The computer-readable medium of claim 19 wherein the first and second values in the set of data correspond to lanes and scan numbers of an electrophoresis gel, and wherein the method includes:

identifying a lane for the test samples in the set of data based on determined lane and scan numbers of the control sample; and

,

identifying scan numbers for the test samples that are within a predetermined stringency amount of the scan number of the control sample.

27. The computer-readable medium of claim 19 wherein the first and second values in the set of data correspond respectively to x-axis and y-axis spatial coordinates and wherein identifying first or second values for at least some of the test samples in the set of data includes identifying x- or y-axis coordinates for the test samples that are within a predetermined amount of the x- or y-axis coordinates of the control sample.

28. A method for displaying to a user information from biological samples, comprising:

receiving a set of data produced from testing a set of biological samples, wherein the biological samples include test samples and at least one control sample related to at least some of the test samples by space, time or frequency, and wherein the set of data includes first and second values and a quantitative value for each test sample;

identifying first or second values corresponding to the control sample in the set of data;

identifying first or second values for at least some of the test samples in the set of data based on the identified first or second values of the control sample and the spatial, temporal or frequency relationship between the control sample and the at least some of the test samples;

filtering the quantitative values for the at least some of the test samples in the set of data based on the identified first or second values;

analyzing each of the test samples by calculating a ratio of a quantitative value of a first component of the first or second value for each test sample to the sum of the quantitative value of the first component and a quantitative value of a second component of the first or second value for each respective test sample; and

displaying the filtered quantitative values, so that only quantitative values for test samples of interest are displayed.

29. The method of claim 28 wherein the identifying of the first or second values for at least some of the test samples includes receiving an indication from the user of the spatial, temporal or frequency relationship to be used for the identifying.

30. The method of claim 28 wherein the filtering of the quantitative values for the at least some of the test samples includes receiving an indication from the user of a slope correction for the quantitative values of the test samples.

31. The method of claim 28 wherein the first and second values in the set of data correspond respectively to lanes and scan numbers from an electrophoresis gel, and wherein the filtering of the quantitative values for the at least some of the test samples includes receiving an indication from the user of a stringency amount for the scan numbers of the test samples.

32. A method for generating information based on biological samples, comprising:

receiving a set of data produced from testing a set of biological samples, wherein the biological samples includes a test sample;

filtering the test sample to separate the test sample into at least first and second components;

analyzing the test sample by calculating a ratio of the quantitative value of the first component to the quantitative value of a sum of the first and second components; and

displaying results of the analysis.

33. The method of claim 32 wherein the first component is extramitochondrial DNA and the second component is mitochondrial DNA.

34. The method of claim 32 wherein the first component is a first type of mitochondrial DNA and the second component is a second type of mitochondrial DNA.

35. The method of claim 32 wherein the set of data produced from testing a set of biological samples includes at least one control sample, the method further comprising:

filtering the control sample in conjunction with filtering the test sample wherein the control sample is related to the first or second components of the test sample by space, time or frequency; and

identifying the first or second components related to the control sample in the set of data, whereby the analysis is performed on a selected one of the first and second identified components.