Systems and methods for run-time sequencing run quality monitoring

• US 9,727,032 B2
• Filed: 12/06/2011
• Issued: 08/08/2017
• Est. Priority Date: 12/14/2010
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Subramaniam, Yerramalli, Suri, Puneet, Chang, Sylvia, Yang, Chengyong
• Primary Examiner(s): Sasaki, Shogo
• Application Number:
  US13/994,661
• Publication Number:
  US 20130331992A1
• Time in Patent Office: 2,072 Days
• CPC Class Codes: B24B 41/062 between centres; Dogs
• CPC Class Codes: B24B 41/065 Steady rests
• CPC Class Codes: B24B 5/04 for grinding cylindrical surfaces externally grinding combined cylindrical and conical surfaces B24B5/14
• CPC Class Codes: G05B 11/01 electric
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids

Abstract

Systems and methods of providing run-time quality control and monitoring of a single or multiple sequencing runs are provided herein. In some embodiments, the run-time system includes or is in communication with a processor capable of determining various types of run-time information relating to the quality, progress, etc. of various sequencing runs. In some embodiments, the system can also be in communication with a user interface, for example, a GUI, capable of representing and communicating various types of information to a user regarding the quality of the individual or multiple runs, the functioning of the instrument, an error event, etc. Additionally, the system can capable of receiving actionable information from a user via the GUI thereby allowing the user to terminate or repeat various sequencing steps in a particular run, terminate a entire run, terminate all runs, allow a run to proceed, etc.

Claims

1. A system for sequencing nucleic acid samples, the system comprising:

a sequencing instrument for interrogating a control set comprising a collection of differing nucleic acids each having a known sequence and known physical properties and a nucleic acid sample for producing control data for the control set and sample data for the nucleic acid sample; and

a processor in communication with the sequencing instrument configured to;

receive the control data and the sample data from the sequencing instrument;

compare an intensity, a relative intensity, or a quality of the control data to an intensity, a relative intensity, or a quality of the sample data;

perform an event handling routine based on the comparison of the intensity, relative intensity, or quality of the control data to the intensity, relative intensity, or quality of the sample data;

determine a required amount of a reagent needed by a sequencing instrument to sequence the nucleic acid sample;

determine an available amount of the reagent;

identify a time at which the sequencing instrument will need an additional amount of the reagent in response to determining that the required amount exceeds the available amount;

notify an operator of the time at which the sequencing instrument will need an additional amount of the reagent;

instruct the sequencing instrument to suspend interrogating the nucleic acid sample prior to the time at which the sequencing instrument will need the additional amount of the reagent; and

instruct the sequencing instrument to resume interrogating the nucleic acid sample in response to determining that the additional amount of the reagent has been added.

2. The system of claim 1, wherein the processor is further configured to determine a control quality value for the control data and a sample quality value for the sample data.

3. The system of claim 2, wherein the processor is further configured to generate a graphical representation of the sample quality value.

4. The system of claim 2, wherein the event handling routine includes providing an event notification.

5. The system of claim 4, wherein providing an event notification includes sending an electronic message.

6. The system of claim 4, wherein providing an event notification includes providing an explanation of the probable cause of an event condition based on comparing the control quality value, the sample quality value, and a threshold.

7. The system of claim 1, wherein the control set comprises a set of solid supports each having a collection of nucleic acids of known sequence and physical properties attached thereto.

8. The system of claim 1, wherein the control set comprises a solid support having a collection of nucleic acids of known sequence and physical properties attached thereto such that each of the nucleic acids is located at a substantially distinct location on the solid support.

9. The system of claim 1, wherein the processor is further configured to determine a control quality value for the control data.

10. The system of claim 1, wherein the processor is further configured to determine a sample quality value for the sample data.

11. The system of claim 4, wherein providing an event notification includes displaying an alert.

12. The system of claim 1, wherein the comparison of the intensity, relative intensity, or quality of the control data to the intensity, relative intensity, or quality of the sample data comprises comparing an intensity of the control data to an intensity of the sample data.

13. The system of claim 1, wherein the comparison of the intensity, relative intensity, or quality of the control data to the intensity, relative intensity, or quality of the sample data comprises comparing a relative intensity of the control data to a relative intensity of the sample data.

14. The system of claim 1, wherein the comparison of the intensity, relative intensity, or quality of the control data to the intensity, relative intensity, or quality of the sample data comprises comparing a quality of the control data to a quality of the sample data.

15. The system of claim 14, wherein the quality of each of the control data and the sample data being compared comprises a probability that the data is not a result of a random or chance event or otherwise false.

16. A computer program product, comprising a non-transitory computer-readable storage medium whose contents include a program with instructions being executed on a processor, the instructions comprising:

instructions to obtain control data for a control set comprising a collection of differing nucleic acids each having a known sequence and known physical properties and sample data for a nucleic acid sample from a sequencing instrument,

instructions to determine a control quality value for the control data and a sample quality value for the sample data;

instructions to compare the control quality value and the sample quality value;

instructions to perform an event handling routine in response to determining that the control quality value or the sample quality value is below a threshold;

instructions to determine a required amount of a reagent needed by a sequencing instrument to sequence the nucleic acid sample;

instructions to determine an available amount of the reagent;

instructions to identify a time at which the sequencing instrument will need an additional amount of the reagent in response to determining that the required amount exceeds the available amount;

instructions to notify an operator of the time at which the sequencing instrument will need an additional amount of the reagent;

instructions to notify the sequencing instrument to suspend interrogating the nucleic acid sample prior to the time at which the sequencing instrument will need the additional amount of the reagent; and

instructions to notify the sequencing instrument to resume interrogating the nucleic acid sample in response to determining that the additional amount of the reagent has been added.

17. The computer program product of claim 16, further comprising instructions to generate a graphical representation of the sample quality value.

18. The computer program product of claim 16, wherein instructions to perform the event handling routine include instructions to provide an event notification.

19. The computer program product of claim 18, wherein instructions to provide an event notification includes instructions to send an electronic message, instructions to display an alert, or any combination thereof.

20. The computer program product of claim 18, wherein the instructions to provide an event notification include instructions to provide an explanation of the probable cause of the event condition based on comparing the control quality value, the sample quality value, and the threshold.