Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results

Abstract

This disclosure provides, among other things, methods for generating and applying therapeutic interventions. The methods involve, for example, (a) sequencing polynucleotides from cancer cells from a subject; (b) identifying and quantifying somatic mutations in the polynucleotides; (c) developing a profile of tumor heterogeneity in the subject indicating the presence and relative quantity of a plurality of the somatic mutations in the polynucleotides, wherein different relative quantities indicates tumor heterogeneity; and (d) determining a therapeutic intervention for a cancer exhibiting the tumor heterogeneity, wherein the therapeutic intervention is effective against a cancer having the profile of tumor heterogeneity determined.

What is claimed is: 
     
         1 . A method for analyzing biomolecular polymers from disease cells from a subject, the method comprising:
 (a) providing a population of biomolecular polymers from disease cells from at least a bodily fluid sample from the subject, wherein a plurality of the biomolecular polymers in the bodily fluid sample comprises cell-free deoxyribonucleic acid (cfDNA) molecules and polypeptide molecules;   (b) performing biomolecular analysis of a plurality of the biomolecular polymers from the population of biomolecular polymers, wherein the biomolecular analysis comprises genomic, epigenetic and proteomic analysis, wherein at least the genomic analysis comprises DNA sequencing;   (c) determining and quantifying biomolecular variants in the biomolecular polymers based on the biomolecular analysis;   (d) developing a profile of disease cell heterogeneity in the and   (e) determining a therapeutic intervention for a disease exhibiting the disease cell heterogeneity, wherein the therapeutic intervention is effective against a disease having the profile of disease cell heterogeneity determined.   
     
     
         2 . The method of  claim 1 , wherein the disease cells are spatially distinct disease cells. 
     
     
         3 . The method of  claim 1 , wherein the epigenetic analysis comprises methylation analysis. 
     
     
         4 . The method of  claim 3 , wherein the methylation analysis comprises conversion of methylated bases followed by the DNA sequencing. 
     
     
         5 . The method of  claim 1 , wherein the proteomic analysis is performed by mass spectrometry. 
     
     
         6 . The method of  claim 1 , wherein the biomolecular polymers further comprise ribonucleic acid (RNA) molecules or cell-free RNA (cfRNA) molecules. 
     
     
         7 . The method of  claim 6 , wherein the biomolecular analysis further comprises RNA expression. 
     
     
         8 . The method of  claim 1 , wherein the bodily fluid sample is blood or urine. 
     
     
         9 . The method of  claim 1 , wherein the biomolecular polymers are comprised in a plurality of biological samples. 
     
     
         10 . The method of  claim 9 , wherein the plurality of biological samples comprise a sample from a solid tumor biopsy. 
     
     
         11 . The method of  claim 9 , wherein the plurality of biological samples comprise a sample selected from the group consisting of blood, serum, tumor cells, saliva, urine, lymphatic fluid, prostatic fluid, seminal fluid, milk, sputum, stool and tears. 
     
     
         12 . The method of  claim 1 , wherein the method comprises monitoring changes in the profile of disease cell heterogeneity over time. 
     
     
         13 . The method of  claim 1 , wherein the disease cells comprise cancer cells. 
     
     
         14 . The method of  claim 13 , comprising using a database to identify the effective therapeutic intervention for a subject having cancer, wherein the database includes, for each of a plurality of subjects having cancer, tumor genomic testing data, including somatic alterations, collected at two or more time intervals per subject, one or more therapeutic interventions administered to each of the subjects at one or more times and efficacy of the therapeutic interventions. 
     
     
         15 . The method of  claim 1 , wherein the profile of disease cell heterogeneity comprises a tumor response map indicating changes over time in genomic, epigenetic and proteomic information from a tumor. 
     
     
         16 . The method of  claim 15 , wherein the tumor response map is generated by (1) normalizing quantitative measures of each of the plurality of variants for rendering across serial time points, and (2) applying a scaling factor to the normalized quantitative measure of each of the plurality of variants. 
     
     
         17 . The method of  claim 16 , wherein the tumor response map is a graphical representation of relative quantities of each of the plurality of variants at each of the serial time points for somatic mutations present at a non-zero quantity and at least one of the serial time points. 
     
     
         18 . The method of  claim 1 , wherein the determining and quantifying biomolecular variants comprises analyzing copy number variation (CNV) mutant allele frequencies and methylation mutant allele frequencies. 
     
     
         19 . The method of  claim 1 , further comprising analzying the genomes of immune cells obtained from the bodily fluid sample of the subject. 
     
     
         20 . The method of  claim 1 , wherein a plurality of the cfDNA molecules are tagged with molecular barcodes and amplified prior to (b).