Abstract: Methods, systems, and software are provided for estimating a circulating tumor fraction (ctFE) for a test subject. Sequence reads are obtained from a panel-enriched sequencing reaction, including sequences for cfDNA fragments corresponding to probe sequences and sequences for cfDNA fragments not corresponding to probe sequences. Bin coverage values are determined from the sequences. Segments are formed by grouping adjacent bins based on similar coverage value and segment coverage values are determined based on bin coverage values for bins mapping to each segment. For each simulated ctFE in a plurality of ctFEs, segments are fitted to an integer copy state by identifying the integer copy state that best matches the segment coverage value. The circulating tumor fraction for the test subject is determined using error optimization between segment coverage values and integer copy states across the simulated ctFEs.

Abstract: Systems and methods for molecular residual disease (MRD) status determination for a subject's cancer condition subject uses sequence reads from methylation sequencing of cell-free DNA fragments from the subject's liquid biopsy sample to determine their methylation patterns. From this, corresponding numbers of circulating-tumor DNA (ctDNA) fragments mapping to each of a plurality of regions of the genome of the subject's species are determined. Corresponding expected numbers of noise fragments in each region are determined based on corresponding distributions using observed sequencing depths and learned background emission rates for each region. An excess fragments per million (FPM) value, corrected by an observed CHG methylation level, is determined from the observed number of ctDNA fragments in excess of the expected number of noise fragments in each region. MRD is called when the CHG corrected excess FPM value satisfies a threshold value, and a call against MRD is made when it does not.

Abstract: Methods, systems, and software are provided for monitoring a cancer condition of a test subject. The method includes obtaining a liquid biopsy sample from the subject at a second time point, occurring after a first time point, containing cell-free DNA fragments. Low-pass whole genome methylation sequencing of the cell-free DNA fragments is performed to obtain nucleic acid sequences having a methylation pattern for a corresponding cell-free DNA fragment. The nucleic acid sequences are mapped to a location on a reference genome. Methylation metrics are determined based on the methylation patterns and mapped locations of the nucleic acid sequences. A circulating tumor fraction is estimated from the methylation metrics, and the estimate is compared to an estimate of the circulating tumor fraction for the test subject at the first time point.

Abstract: A method and system comprising storing a set of user application programs each requiring an application specific subset of data to perform application processes and generate a respective genomic variant characterization for each of a plurality of patients with cancerous cells and receiving cancer treatment. The method including, obtaining clinical records data including cancer related information, generating genomic sequencing data for the patient's cancerous cells and normal cells, shaping at least a subset of the genomic sequencing data to generate system structured data. Storing the system structured data in a first database, selecting the application specific data from the first database, storing the application specific data in a second database for application program interfacing, receiving the respective genomic variant characterization from the user application program, and storing the genomic variant characterization from the user application program in a third database.

Abstract: A method for identifying actionable care events includes receiving data sources relating to a subject; storing data from them in a first database; generating a database comprising structured data fields and metadata fields from the sources; generating output data related to fields within the data or metadata fields; populating the database with the output data; generating criteria sets corresponding to respective actionable care events; evaluating the generated database using the criteria sets; identifying whether any of the criteria sets are not sufficiently satisfied by the database, wherein an underlying error or an indication of missing or incomplete information within the database with respect to a criteria set indicates a corresponding actionable care event; determining that other data sources within the collection do not sufficiently satisfy any of the identified criteria sets; and generating, based on the identifying and determining, a notification that at least one actionable care event applies.

Abstract: A method includes displaying a cohort report; receiving a request to determine a therapy identification; causing information to be transmitted to a remote cloud server; receiving clinical trial data; and updating the cohort report. A computing system includes a processor; and a memory having stored thereon computer-executable instructions that, when executed by the one or more processors, cause the computing system to: display a cohort report; receive a request to determine a therapy identification; cause information to be transmitted to a remote cloud server; receive clinical trial data; and update the cohort report. A computer-readable medium having stored thereon a set of computer-executable instructions that, when executed by one or more processors, cause a computer to: display a cohort report; receive a request to determine a therapy identification; cause information to be transmitted to a remote cloud server; receive clinical trial data; and update the cohort report.

Abstract: A method for data intake and consumption includes the steps of: storing a plurality of micro-service programs, operational user application programs, and analytical user application programs in at least one computer system, storing system data received from a plurality of different sources in a database, the system data includes clinical records data in original forms, the clinical records data including cancer state information, treatment types, and treatment efficacy information, consuming, by each of the micro-service programs, defined subsets of the system data to generate a new data product, storing the new data product in a second database, and consuming the new data product by others of the micro-service programs or the operational or analytical user application programs.

Abstract: A method and system for storing user application programs and micro-service programs, for each of multiple patients that have cancerous cells and receive treatment, includes obtaining clinical records data in original forms, storing it in a semi-structured first database, generating sequencing data for the patient's cancerous and normal cells using a next generation genomic sequencer, storing the sequencing data in the first database, shaping at least some of the first database data to generate system structured data optimized for searching and including clinical record data, storing the structured data in a second database, for each user application program, selecting an application-specific subset of data from the second database and storing it in a structure optimized for application program interfacing in a third database, wherein an orchestration manager operatively connected to one or more micro-service programs receives status messages and initiates a respective micro-service program when program prere

Abstract: A method and system comprising storing a set of user application programs each requiring an application specific subset of data to perform application processes and generate a respective genomic variant characterization for each of a plurality of patients with cancerous cells and receiving cancer treatment. The method including, obtaining clinical records data including cancer related information, generating genomic sequencing data for the patient's cancerous cells and normal cells, shaping at least a subset of the genomic sequencing data to generate system structured data. Storing the system structured data in a first database, selecting the application specific data from the first database, storing the application specific data in a second database for application program interfacing, receiving the respective genomic variant characterization from the user application program, and storing the genomic variant characterization from the user application program in a third database.

Abstract: Methods, systems, and software are provided for determining whether a subject is afflicted with an oncogenic pathogen. Nucleic acids from a biological sample of the subject are hybridized to a probe set that includes probes for human genomic loci and for genomic loci of oncogenic pathogens. Sequence reads of the hybridized nucleic acid are obtained and it’s determined whether each sequence read aligns to a human reference genome. For each sequence read that fails to align to the human reference genome, it’s determined whether the sequence read aligns to a reference genome of an oncogenic pathogen. Sequence reads that both (i) fail to align to the human reference genome and (ii) align to a reference genome of an oncogenic pathogen are tracked, thereby obtaining a sequence read count for the oncogenic pathogen. The sequence read count is used to ascertain whether the subject is afflicted with the oncogenic pathogen.

Abstract: A system, method, and mobile device application are configured to capture, with a mobile device, a document such as a next generation sequencing (NGS) report that includes NGS medical information about a genetically sequenced patient. The method includes receiving, from a mobile device, an image of a medical document comprising NGS medical information of the patient, extracting a first region from the image, extracting NGS medical information of the patient from the first region into a structured dataset, the extracted NGS medical information including at least one RNA expression, correlating a portion of the extracted NGS medical information that includes the at least one RNA expression with summarized medical information from a cohort of patients similar to the patient, and generating, for display on the mobile device, a clinical decision support report comprising the summarized medical information.

Abstract: A method and system for conducting genomic sequencing, the method comprising storing a set of user application programs wherein each of the programs requires an application specific subset of data, for each of a plurality of patients that have cancerous cells and that receive cancer treatment, obtaining clinical records data in original forms including cancer state information, treatment types and treatment efficacy information, storing the clinical records data in a semi-structured first database, for each patient, using a genomic sequencer to generate genomic sequencing data for the patient's cancerous cells and normal cells, storing the sequencing data in the first database, shaping at least a subset of the first database data to generate system structured data including clinical record data and sequencing data wherein the system structured data is optimized for searching, storing the system structured data in a second database, for each user application program, selecting the application specific subset o

Abstract: Methods, systems, and software are provided for validating a somatic sequence variant in a subject having a cancer condition. Sequence reads are obtained from sequencing cell-free DNA fragments in a liquid biopsy sample of the subject. Sequence reads are aligned to a reference sequence. A variant allele fragment count and locus fragment count are identified for a candidate variant that maps to a locus in the reference sequence. The variant allele fragment count is compared against a dynamic variant count threshold for the locus. The threshold is based on a pre-test odds of a positive variant call for the locus, based on the prevalence of variants in a genomic region including the locus in a cohort of subjects having the cancer condition. The somatic sequence variant in the subject is validated, or rejected, when the variant allele fragment count for the candidate variant satisfies, or does not satisfy, the threshold.

Abstract: Methods, systems, and software are provided for monitoring a cancer condition of a test subject. The method includes obtaining a liquid biopsy sample from the subject at a second time point, occurring after a first time point, containing cell-free DNA fragments. Low-pass whole genome methylation sequencing of the cell-free DNA fragments is performed to obtain nucleic acid sequences having a methylation pattern for a corresponding cell-free DNA fragment. The nucleic acid sequences are mapped to a location on a reference genome. Methylation metrics are determined based on the methylation patterns and mapped locations of the nucleic acid sequences. A circulating tumor fraction is estimated from the methylation metrics, and the estimate is compared to an estimate of the circulating tumor fraction for the test subject at the first time point.

Abstract: Methods, systems, and software are provided for validating a copy number variation in a test subject. A first dataset is obtained comprising bin-level sequence ratios, segment-level sequence ratios and segment-level measures of dispersion. Bins representing regions of a human reference genome are determined from sequencing cell-free nucleic acids in a liquid biopsy sample and reference samples. Segments encompass subsets of adjacent bins, where segment-level sequence ratios and measures of dispersion are determined using bin-level sequence ratios. A copy number status annotation for a segment is validated by applying the first dataset to a plurality of filters comprising a measure of central tendency bin-level sequence ratio filter, a confidence filter, and a measure of central tendency-plus-deviation bin-level sequence ratio filter. When a filter is fired, the copy number status annotation of the segment is rejected; and when no filter is fired, the copy number status annotation of the segment is validated.

Abstract: Methods, systems, and software are provided for validating a somatic sequence variant in a subject having a cancer condition. Sequence reads are obtained from sequencing cell-free DNA fragments in a liquid biopsy sample of the subject. Sequence reads are aligned to a reference sequence. A variant allele fragment count and locus fragment count are identified for a candidate variant that maps to a locus in the reference sequence. The variant allele fragment count is compared against a dynamic variant count threshold for the locus. The threshold is based on a pre-test odds of a positive variant call for the locus, based on the prevalence of variants in a genomic region including the locus in a cohort of subjects having the cancer condition. The somatic sequence variant in the subject is validated, or rejected, when the variant allele fragment count for the candidate variant satisfies, or does not satisfy, the threshold.

Abstract: Methods, systems, and software are provided for estimating a circulating tumor fraction for a test subject. Sequence reads are obtained from a panel-enriched sequencing reaction, including sequences for a first plurality of cfDNA fragments corresponding to probe sequences and a second plurality of cfDNA fragments not corresponding to probe sequences. Bin-level coverage ratios are determined from the sequences. Segments are formed by grouping adjacent bins based on similar coverage ratios and segment-level coverage ratios are determined based on bin-level coverage ratios for bins in the segment. For each simulated circulating tumor fraction in a plurality of circulating tumor fractions, segments are fitted to an integer copy state by identifying the integer copy state that best matches the segment-level coverage ratio.

Abstract: Methods, systems, and software are provided for estimating a circulating tumor fraction for a test subject. Sequence reads are obtained from a panel-enriched sequencing reaction, including sequences for a first plurality of cfDNA fragments corresponding to probe sequences and a second plurality of cfDNA fragments not corresponding to probe sequences. Bin-level coverage ratios are determined from the sequences. Segments are formed by grouping adjacent bins based on similar coverage ratios and segment-level coverage ratios are determined based on bin-level coverage ratios for bins in the segment. For each simulated circulating tumor fraction in a plurality of circulating tumor fractions, segments are fitted to an integer copy state by identifying the integer copy state that best matches the segment-level coverage ratio.

Abstract: Methods, systems, and software are provided for validating a copy number variation in a test subject. A first dataset is obtained comprising bin-level sequence ratios, segment-level sequence ratios and segment-level measures of dispersion. Bins representing regions of a human reference genome are determined from sequencing cell-free nucleic acids in a liquid biopsy sample and reference samples. Segments encompass subsets of adjacent bins, where segment-level sequence ratios and measures of dispersion are determined using bin-level sequence ratios. A copy number status annotation for a segment is validated by applying the first dataset to a plurality of filters comprising a measure of central tendency bin-level sequence ratio filter, a confidence filter, and a measure of central tendency-plus-deviation bin-level sequence ratio filter. When a filter is fired, the copy number status annotation of the segment is rejected; and when no filter is fired, the copy number status annotation of the segment is validated.

Abstract: Methods, systems, and software are provided for monitoring a cancer condition of a test subject. The method includes obtaining a liquid biopsy sample from the subject at a second time point, occurring after a first time point, containing cell-free DNA fragments. Low-pass whole genome methylation sequencing of the cell-free DNA fragments is performed to obtain nucleic acid sequences having a methylation pattern for a corresponding cell-free DNA fragment. The nucleic acid sequences are mapped to a location on a reference genome. Methylation metrics are determined based on the methylation patterns and mapped locations of the nucleic acid sequences. A circulating tumor fraction is estimated from the methylation metrics, and the estimate is compared to an estimate of the circulating tumor fraction for the test subject at the first time point.