Granted Patent
B2
US 12,620,454 · App. 17/466,606 · Granted May 5, 2026
BAMBAM: parallel comparative analysis of high-throughput sequencing data
G16B30/10C12Q1/6886G06F3/04845G06F40/169G06N7/01G06T11/26G16B20/20G16B30/00G16B40/00G16H50/20C12Q2600/106C12Q2600/118C12Q2600/156G06F2203/04806G16H10/40G16H10/60G16H70/20Y02A90/10Y02A90/30
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Abstract
The present invention relates to methods for evaluating and/or predicting the outcome of a clinical condition, such as cancer, metastasis, AIDS, autism, Alzheimer's, and/or Parkinson's disorder. The methods can also be used to monitor and track changes in a patient's DNA and/or RNA during and following a clinical treatment regime. The methods may also be used to evaluate protein and/or metabolite levels that correlate with such clinical conditions. The methods are also of use to ascertain the probability outcome for a patient's particular prognosis.
Claims (36)
1 . A computer-based method of variant calling from at least one tissue sample, the method comprising:
(a) retrieving, at a same time from each of at least two BAM/SAM files stored in a first storage device while keeping each file in synchrony, only a set of aligned short reads of genomic sequence data associated with a respective pileup, each set of aligned short reads being retrieved by a computer processor coupled with a computer readable memory, wherein each set of aligned short reads overlap a given common genomic position of a reference sequence;
(b) storing, in the computer readable memory, each retrieved set of aligned short reads of genomic sequence data, all the stored aligned short reads overlapping the given common genomic position;
(c) calculating, via the computer processor coupled with the computer readable memory, a probability of an allele at the given common genomic position as a function of a number of observed alleles in the aligned short reads of the respective pileup while incorporating a base error rate of a sequencer;
(d) repeating (a)-(c) for each of additional given common genomic positions using additional sets of aligned short reads, wherein the sets of aligned short reads represent at least 10% of a genome, transcriptome, or proteome of the at least one tissue sample; and
(e) storing in a second storage device a variant supported by the allele at at least one of the given common genomic positions.
2 . The method of claim 1 , wherein the allele represents at least one of a germline allele and a tumor allele.
3 . The method of claim 2 , further comprising calculating the probability as a function of a base probability from at least one of two parental alleles and the number of observed alleles in the aligned short reads of the respective pileup.
4 . The method of claim 1 , wherein the allele comprises an allele-specific copy number.
5 . The method of claim 4 , further comprising expanding or contracting an analysis window around the given common genomic position.
6 . The method of claim 4 , further comprising calculating the allele-specific copy number as a function of a number of supporting aligned short reads.
7 . The method of claim 4 , further comprising calculating the allele-specific copy number at the given common genomic position, wherein the given common genomic position has at least two different alleles.
8 . The method of claim 7 , wherein the allele-specific copy number comprises a majority allele count.
9 . The method of claim 7 , wherein the allele-specific copy number comprises a minority allele count.
10 . The method of claim 4 , further comprising identifying a loss of heterozygosity at least at the given common genomic position as a function of the allele-specific copy number.
11 . The method of claim 10 , wherein the loss of heterozygosity is associated with at least a region of the genome.
12 . The method of claim 1 , wherein the allele is selected as supporting the variant based on an allelic imbalance at the given common genomic position.
13 . The method of claim 1 , wherein the allele is selected as supporting the variant regardless of an allelic proportion.
14 . The method of claim 1 , wherein the allele comprises an allelic state.
15 . The method of claim 14 , wherein the allelic state represents homozygosity.
16 . The method of claim 1 , further comprising estimating an amount of a contaminant in the at least one tissue sample as a function of a hemizygous loss.
17 . The method of claim 16 , wherein the hemizygous loss is based on an allele-specific copy number.
18 . The method of claim 17 , wherein the contaminant comprises a normal contaminant in the at least one tissue sample.
19 . The method of claim 17 , wherein the contaminant comprises a normal contaminant in a tumor tissue sample.
20 . The method of claim 1 , wherein the at least one tissue sample comprises a normal tissue sample.
21 . The method of claim 20 , wherein the normal tissue sample comprises a blood sample.
22 . The method of claim 1 , wherein the at least one tissue sample comprises a diseased tissue sample.
23 . The method of claim 22 , wherein the diseased tissue sample comprises a tumor tissue sample.
24 . The method of claim 1 , wherein the respective pileup comprises at least 30 short reads.
25 . The method of claim 1 , wherein the aligned short reads comprise polynucleotide sequences.
26 . The method of claim 25 , wherein the aligned short reads comprise DNA sequences.
27 . The method of claim 1 , wherein the aligned short reads comprise RNA sequences.
28 . The method of claim 27 , wherein the RNA sequences include at least one of the following: mRNA transcript, rRNA, or tRNA sequences.
29 . The method of claim 1 , wherein the at least one tissue sample is a sample from at least one of the following: a rat, a dog, a mouse, a primate, an animal, a plant, and a human.
30 . The method of claim 1 , wherein the at least one tissue sample includes at least two samples.
31 . The method of claim 30 , wherein the at least two samples includes at least three samples.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 3, 2021
From: SANBORN, JOHN ZACHARY; HAUSSLER, DAVID
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 057384/0674 →
Continuity (5)
Provisional Application
61396356
· May 25, 2010
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