BAMBAM: parallel comparative analysis of high-throughput sequencing data

1. A method of analyzing a differential genetic sequence object of a person, the method comprising:

storing a reference differential genetic sequence object in a medical records database that is informationally coupled to a computer system;

storing, by the computer system, a first file of tumor reads obtained from tumor tissue of the person, the tumor reads covering a sequence of genomic positions;

storing, by the computer system, a second file of matched normal reads obtained from matched normal tissue of the person, the matched normal reads covering the sequence of genomic positions;

for each genomic position of the sequence of genomic positions:

reading, into RAM of the computer system, a set of the tumor reads overlapping the genomic position;

reading, into RAM of the computer system, a set of the matched normal reads overlapping the genomic position; and

comparing, by the computer system, the set of the tumor reads to the set of the matched normal reads, thereby determining a plurality of local differential strings comprising differences between the tumor tissue and the matched normal tissue for the sequence of genomic positions;

generating, by the computer system, the differential genetic sequence object of the person using the plurality of local differential strings;

calculating, by the computer system, a deviation between the plurality of local differential strings in the differential genetic sequence object of the person and a plurality of local differential strings in the reference differential genetic sequence object to produce a deviation record; and

using, by the computer system, the deviation record to generate a person-specific deviation profile.

2. The method of claim 1 wherein the reference differential genetic sequence object is calculated from a plurality of local differential strings of the person.

3. The method of claim 1 , further comprising:

producing a patient-specific instruction based on the person-specific deviation profile.

4. The method of claim 3 , wherein the patient-specific instruction includes a recommendation for a treatment strategy.

5. The method of claim 1 , wherein generating the person-specific deviation profile comprises:

comparing the deviation record to a population analysis record.

6. The method of claim 5 , wherein the population analysis record is determined from a plurality of local differential strings of a plurality of reference differential genetic sequence objects of members sharing a common feature.

7. The method of claim 6 , wherein the common feature is a treatment history or treatment success.

8. The method of claim 5 , wherein comparing the deviation record to the population analysis record identifies the person as belonging to a specified population.

9. The method of claim 1 , wherein the person-specific deviation profile indicates a risk of developing a disease.

10. The method of claim 1 , wherein the reference differential genetic sequence object comprises metadata indicating a responsiveness to treatment.

11. A system for analyzing a differential genetic sequence object of a person, the system comprising:

a medical records database storing (i) a reference differential genetic sequence object, (ii) a first file of tumor reads obtained from tumor tissue of the person, the tumor reads covering a sequence of genomic positions, and (iii) a second file of matched normal reads obtained from matched normal tissue of the person, the matched normal reads covering the sequence of genomic positions;

a computer system configured to perform:

for each genomic position of the sequence of genomic positions:

reading, into RAM of the computer system, a set of the tumor reads overlapping the genomic position;

reading, into RAM of the computer system, a set of the matched normal reads overlapping the genomic position; and

comparing the set of the tumor reads to the set of the matched normal reads, thereby determining a plurality of local differential strings comprising differences between the tumor tissue and the matched normal tissue for the sequence of genomic positions;

generating the differential genetic sequence object of the person using the plurality of local differential strings;

calculating a deviation between the plurality of local differential strings in the differential genetic sequence object of the person and a plurality of local differential strings in the reference differential genetic sequence object to produce a deviation record; and

using the deviation record to generate a person-specific deviation profile.

12. The system of claim 11 , wherein the computer system is further configured to perform:

producing a patient-specific instruction based on the person-specific deviation profile.

13. The system of claim 12 , wherein the patient-specific instruction includes a recommendation for a treatment strategy.

14. The system of claim 11 , wherein generating the person-specific deviation profile comprises:

comparing the deviation record to a population analysis record.

15. The system of claim 14 , wherein the population analysis record is determined from a plurality of local differential strings of a plurality of reference differential genetic sequence objects of members sharing a common feature.

16. The system of claim 15 , wherein the common feature is a treatment history or treatment success.

17. The system of claim 14 , wherein comparing the deviation record to the population analysis record identifies the person as belonging to a specified population.

18. The system of claim 11 , wherein the person-specific deviation profile indicates a risk of developing a disease.

19. The system of claim 11 , wherein the reference differential genetic sequence object comprises metadata indicating a responsiveness to treatment.