Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.

The present disclosure relates generally to methods and compositions for cancer immunotherapy, and more specifically, liquid markers for predicting effectiveness of cancer therapies. The disclosure features compositions and methods that are useful for predicting the efficacy of cancer treatment (e.g., a checkpoint inhibitor immunotherapy) and, in some embodiments, administering the cancer treatment such as immunotherapy.

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter. In some implementations, information from fragments of different sizes are used to evaluate copy number variations. In some implementations, one or more t-statistics obtained from coverage information of the sequence of interest is used to evaluate copy number variations. In some implementations, one or more fetal fraction estimates are combined with one or more t-statistics to determine copy number variations.

Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter. In some implementations, information from fragments of different sizes are used to evaluate copy number variations. In some implementations, one or more t-statistics obtained from coverage information of the sequence of interest is used to evaluate copy number variations. In some implementations, one or more fetal fraction estimates are combined with one or more t-statistics to determine copy number variations.

An improved diagnostic assay and methods relating to the same that are directed to mutation focused disease diagnosis and surveillance biomarker panels wherein potential genomic regions are selected based on their ability to encompass the genomic diversity of a patient population, maximize the number of unique markers monitored within each patient are maximized while balancing these factors with empirical sequencing performance, geographic clustering of events with a region across diverse patients, and size and cost associated with measuring the respective genomic region. The methods also include quality control steps to reduce noise and

An improved diagnostic assay and methods relating to the same that are directed to mutation focused disease diagnosis and surveillance biomarker panels wherein potential genomic regions are selected based on their ability to encompass the genomic diversity of a patient population, maximize the number of unique markers monitored within each patient are maximized while balancing these factors with empirical sequencing performance, geographic clustering of events with a region across diverse patients, and size and cost associated with measuring the respective genomic region. The methods also include quality control steps to reduce noise and

The invention is directed to methods for selecting a treatment option for an activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) subject, a germinal center B cell-like diffuse large B cell lymphoma (GCB DLBCL) subject, a primary mediastinal B cell lymphoma (PMBL) subject, a Burkitt lymphoma (BL) subject, or a mantle cell lymphoma (MCL) subject by analyzing digital gene expression data obtained from the subject, e.g., from a biopsy sample.

The invention is directed to methods for selecting a treatment option for an activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) subject, a germinal center B cell-like diffuse large B cell lymphoma (GCB DLBCL) subject, a primary mediastinal B cell lymphoma (PMBL) subject, a Burkitt lymphoma (BL) subject, or a mantle cell lymphoma (MCL) subject by analyzing digital gene expression data obtained from the subject, e.g., from a biopsy sample.