Methods and computer program products for compression of sequencing data

• US 9,515,676 B2
• Filed: 01/30/2013
• Issued: 12/06/2016
• Est. Priority Date: 01/31/2012
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Sugnet, Charles, Cawley, Simon, Gupta, Mohit, Marjanovic, Iztok, Rearick, Todd, Beauchemin, Mark, Hubbell, Earl
• Primary Examiner(s): Brusca, John S
• Application Number:
  US13/754,566
• Publication Number:
  US 20130231870A1
• Time in Patent Office: 1,406 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: H03M 7/30 Compression speech analysis-synthesis for redundancy reduction G10L19/00; for image communication H04N; Expansion; Suppression of unnecessary data, e.g. redundancy reduction

Abstract

A compression method includes measuring a waveform associated with a chemical event occurring on a sensor array, wherein the waveform comprises at least one region associated with expected measured values and at least one region associated with unpredictable measured values; applying a first compression process to the waveform, the first compression process including an averaging of one or more frames in one or more portions of the waveform; and applying a second compression process to the waveform, the second compression process including a truncating of data corresponding to a portion of the waveform that is not related to a nucleotide incorporation component of the waveform.

Claims

1. A compression method, comprising:

measuring a waveform associated with a chemical event occurring on a sensor array, the measuring including digitizing voltage signals using an analog to digital converter to produce a plurality of frames of measured values for the waveform, the voltage signals generated by the sensor array in response to the chemical event, wherein the chemical event is indicative of a number of nucleotide incorporations in a genetic sequencing reaction, wherein the waveform comprises at least one region associated with expected measured values and at least one region associated with unpredictable measured values;

applying a first compression process to the waveform using a processor, the first compression process including an averaging of one or more frames in one or more portions of the waveform to form frame-averaged data, wherein a number of frames of frame-averaged data is less than a number of frames in the plurality of frames of measured values;

applying a keyframe delta compression to the frame-averaged data using the processor, wherein the keyframe delta compression comprises calculating a difference between a current frame of the frame-averaged data and a previous frame of the frame-averaged data associated with the waveform;

forming a compressed data structure including a keyframe of the frame-averaged data and a plurality of the calculated differences subsequent to the keyframe, wherein the compressed data structure represents the keyframe and the plurality calculated differences in a number of bytes that is less than an original number of bytes representing the frame-averaged data;

determining compression information corresponding to one or more compressed data structures;

storing the compression information and the one or more compressed data structures in a memory; and

applying a second compression process to the waveform using the processor, the second compression process including a truncating of data corresponding to a portion of the waveform that is not related to a nucleotide incorporation component of the waveform.

2. The method of claim 1, wherein the truncating of data comprises determining, for each of a plurality of sensors in the sensor array, a cut-off time point for the waveform for that sensor defining a data range to be truncated.

3. The method of claim 2, wherein each cut-off time point is determined by mining a plurality of past analysis runs for a given sensor array geometry.

4. The method of claim 2, wherein each cut-off time point is determined prior to every run or during a calibration procedure.

5. The method of claim 2, wherein each cut-off time point is factory pre-determined for a given sensor array geometry.

6. The method of claim 2, wherein the sensors are arranged in a plurality of regions in the sensor array, and wherein each cut-off time point for sensors in a given region is determined to have a common cut-off time point for sensors in that region.

7. The method of claim 6, wherein each common cut-off time point is determined by finding a best fit to a linear hinge model on a median trace for a region.

8. The method of claim 1, wherein the averaging comprises:

applying a first frame averaging to the at least one portion associated with the expected measured values, wherein the first frame averaging comprises averaging a first number of frames during the at least one portion associated with the expected measured values; and

applying a second frame averaging to the at least one portion associated with the unpredictable measured values, wherein the second frame averaging comprises averaging a second number of frames during the at least one portion associated with the unpredictable measured values, the second number of frames being lower than the first number of frames.

9. The method of claim 8, further comprising:

applying a third frame averaging to a second portion of the waveform, wherein the second portion is associated with another portion of the waveform with expected measured values, and wherein the third frame averaging comprises averaging a third number of frames during the second portion, the third number of frames being higher than the second number of frames; and

applying the keyframe delta compression to the frame-averaged data resulting from the first, second, and third frame averaging.

10. The method of claim 1, wherein the measuring the waveform comprises measuring the waveform of a dynamic response of an ion-sensitive field effect transistor (ISFET) array to a change in ionic strength of an analyte solution in fluid contact with the ISFET array.

11. The method of claim 10, wherein the measuring the waveform of the dynamic response of the ISFET array comprises associating the at least one portion with the unpredictable measured values to a stepwise increase in ion concentration in the analyte solution and associating the at least one portion with the expected measured values to at least one portion of the dynamic response outside of the stepwise increase in ion concentration.

12. The method of claim 11, wherein the averaging comprises applying a first frame averaging to the at least one portion associated with the expected measured values, wherein the first frame averaging comprises averaging a first number of frames during the at least one portion associated with the expected measured values, wherein the first number of frames results from measured values during the at least one portion of the dynamic response outside of the stepwise increase in ion concentration.

13. The method of claim 12, wherein the averaging comprises applying a second frame averaging to the at least one portion associated with the unpredictable measured values, wherein the second frame averaging comprises averaging a second number of frames during the at least one portion associated with the unpredictable measured values, wherein the second number of frames results from measured values during the stepwise increase in ion concentration in the analyte solution.

14. The method of claim 1, wherein the compression information includes the number of bytes for storing each of the one or more compressed data structures.

15. The method of claim 14, wherein the compression information includes a code indicating a change in the number of bytes for storing the one or more compressed data structures from a previous compressed data structure.

16. A computer program product comprising a computer-usable medium having computer program logic recorded thereon that, when executed by one or more processors, compresses data from a sensor array, wherein the data comprise digitized voltage signals generated by the sensor array in response to a chemical event occurring on the sensor array to produce a plurality of frames of measured values of a waveform, wherein the chemical event is indicative of a number of nucleotide incorporations in a genetic sequencing reaction, the computer program logic comprising:

first computer readable program code that enables a processor to obtain the plurality of frames of measured values of the waveform associated with the chemical event occurring on the sensor array, wherein the waveform comprises at least one portion associated with expected measured values and at least one portion associated with unpredictable measured values;

second computer readable program code that enables the processor to apply a first compression process to the waveform, the first compression process including an averaging of one or more frames in one or more portions of the waveform to form frame-averaged data, wherein a number of frames of the frame-averaged data is less than a number of frames in the plurality of frames of measured values;

third computer readable program code that enables the processor to;

apply a keyframe delta compression to the frame-averaged data, wherein the keyframe delta compression comprises calculating a difference between a current frame of the frame-averaged data and a previous frame of the frame-averaged data associated with the waveform,

form a compressed data structure including a keyframe of the frame-averaged data and a plurality of the calculated differences subsequent to the keyframe, wherein the compressed data structure represents the keyframe and the plurality calculated differences in a number of bytes that is less than an original number of bytes representing the frame-averaged data,

determine compression information corresponding to one or more compressed data structures, and

store the compression information and the one or more compressed data structures in a memory; and

fourth computer readable program code that enables the processor to apply a second compression process to the waveform, the second compression process including a truncating of data corresponding to a portion of the waveform that is not related to a nucleotide incorporation component of the waveform.

17. A method for compressing nucleic acid sequencing data, comprising:

obtaining, at a processor, raw data comprising digitized voltage signals from a semiconductor-based genetic sequencing sensor array comprising a plurality of sensors during a data acquisition time period, the raw data comprising at least a non-informative portion corresponding to a subinterval of the data acquisition time period having a location within the data acquisition time period that varies for different sensors according to a position of the sensor in the sensor array;

transforming, using the processor, the raw data into compressed data using both a lossless compression process including a keyframe delta compression process and lossy compression processes including a variable frame averaging process and a data truncation process, the data truncation process being related for each sensor to the position of the sensor in the sensor array and configured to discard the non-informative portion of the raw data, wherein the variable frame averaging process produces variable frame-averaged data, wherein the keyframe delta compression process comprises;

calculating a difference between a current frame of variable frame-averaged data and a previous frame of the variable frame-averaged data

forming a compressed data structure comprising a keyframe of the variable frame-averaged data and a plurality of the calculated differences subsequent to the keyframe, wherein the compressed data structure represents the keyframe and the plurality calculated differences in a number of bytes that is less than an original number of bytes representing the variable frame-averaged data;

determining compression information corresponding to one or more compressed data structures; and

storing the compression information and the one or more compressed data structures in a memory.

18. The method of claim 17, wherein the data truncation process comprises determining, for each of the plurality of sensors in the sensor array, a cut-off time point for that sensor defining the non-informative portion of the raw data to be truncated.

19. The method of claim 18, wherein each cut-off time point is determined by mining a plurality of past analysis runs for a given sensor array geometry.

20. The method of claim 18, wherein the plurality of sensors in the sensor array are arranged in a plurality of regions in the sensor array, and wherein each cut-off time point for sensors in a given region is determined to have a common cut-off time point for sensors in that region.