Abstract: Methods and systems for classifying a patient sample as having a mutation in a BRCA1 or BRCA2 gene or as having genomic structural abnormalities indicating a similar level of homologous recombination deficiency (HRD) as that caused by a mutation in a BRCA1 or BRCA2 gene based on copy number variation determined from next generation sequencing (NGS).

Abstract: Cell free nucleic acid tests are performed using concurrent analysis of cfTNA and cfRNA fractions obtained from the same sample. In preferred embodiments, cfTNA isolation includes isolation of even small fragments of cfDNA and cfRNA, and after reverse transcription of the cfRNA in both fractions, so obtained cDNA libraries are subjected to target enrichment using tiled enrichment oligonucleotides. Most notably, sequence analysis that uses data sets from both cDNA libraries provides heretofore unrealized sensitivity and specificity.

Abstract: Cell free nucleic acid tests are performed using concurrent analysis of cfTNA and cfRNA fractions obtained from the same sample. In preferred embodiments, cfTNA isolation includes isolation of even small fragments of cfDNA and cfRNA, and after reverse transcription of the cfRNA in both fractions, so obtained cDNA libraries are subjected to target enrichment using tiled enrichment oligonucleotides. Most notably, sequence analysis that uses data sets from both cDNA libraries provides heretofore unrealized sensitivity and specificity.

Abstract: A novel classification strategy is described for forecasting clinical outcomes of Diffuse Large B-cell Lymphoma using targeted RNA sequencing combined with machine learning algorithms. The novel method classifies subjects with DLBCL into subgroups based on the clinical course of their disease and expected survival, rather than on Cell of Origin. To focus on survival, the methods first deploy machine learning and divide the subjects into subgroups based on their overall survival. A modified Bayesian classifier is then used to select genes that can forecast various survival groups, followed by validation of these biomarkers using an independent set of clinical cases. This novel approach for stratifying subjects with DLBCL based on the clinical outcome of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy can be used to select high responders and low responders to R-CHOP. Low responders may be offered additional or alternative therapies to improve their survival.

Abstract: A method of treating diffuse large B-cell lymphoma, comprises obtaining a sample from a patient having diffuse large B-cell lymphoma; detecting in the sample, by an assay, mutation in each gene in a first panel; quantifying in the sample an expression level of each gene in a second panel; classifying the diffuse large B-cell lymphoma of the patient as having a cell of origin of either (i) germinal-center B-cell-like or (ii) activated B-cell-like; and treating the patient with a cancer treatment therapy regime. The first panel comprises at least one gene selected from the group consisting of EZH1 and MYD88; and the second panel comprises at least one gene selected from the group consisting of IRF4, MYBL1, RASGRF1, S1PR2 and SSBP2.