Abstract: Disclosed herein are systems, methods, and compositions for identifying subjects likely to respond to an immune oncology therapy. The disclosed methods may include applying one or more model components to a machine learning algorithm. The one or more model components are derived from RNA and/or DNA sequencing from a subject and may include a checkpoint related gene signature, an immune exhaustion signature, a immune oncology signature, a tumor mutational burden, or a granulocytic myeloid derived suppressor cell signature.

Abstract: Described herein are methods for evaluating and improving performance of a genetic screening test for determining a fetal chromosomal abnormality in a test chromosome in a fetus by analyzing a maternal sample of a woman carrying the fetus. The method may include generating simulated maternal samples based on a determined relationship between values of statistical significance and abnormality classifications for the test chromosome of a plurality of reference maternal samples. The method may also include determining specificity values and sensitivity values for a range of abnormality classifier values for the test chromosome based on values of statistical significance and abnormality classifications for the plurality of reference maternal samples and the plurality of simulated maternal samples. A receiver operating characteristic (ROC) curve for the genetic screening test may be generated based on the determined specificity values and sensitivity values.

Abstract: High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduces sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are sequencing adapters comprising a nondegenerate or variable length molecular barcode and compositions comprising a plurality of sequencing adapters, which can be useful for sequencing nucleic acids. Further provided are methods of using the sequencing adapters, including methods of sequencing nucleic acids, methods of identifying an error in a nucleic acid sequence, and methods of determining the number of nucleic acid molecules in a library.

Abstract: High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduces sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are sequencing adapters comprising a nondegenerate or variable length molecular barcode and compositions comprising a plurality of sequencing adapters, which can be useful for sequencing nucleic acids. Further provided are methods of using the sequencing adapters, including methods of sequencing nucleic acids, methods of identifying an error in a nucleic acid sequence, and methods of determining the number of nucleic acid molecules in a library.

Abstract: A system and method for determining a respective carrier status of an individual is provided. In one implementation, a method includes training a neural network model based on predetermined information related to at least one genetic variant and determining the respective carrier status based on a normalized read depth for the gene in a genome of the individual and allele dosage data for the gene using a machine learning algorithm. The method is configured to receive, as inputs, the normalized read depth and allele dosage data, and output the respective carrier status of the individual for the at least one genetic variant. In another implementation a system includes a recurrent neural network. The recurrent neural network includes a plurality of long short-term memory (LSTM) network cells linked sequentially in the recurrent neural network, a plurality of layers of long short-term memory (LSTM) network cells; and a fully connected sigmoid module.

Abstract: Methods for determining a respective carrier status of an individual are disclosed. In some examples, the method includes determining the respective carrier status based on copy number data for a gene in a genome of the individual and SNP data for the gene using a machine learning algorithm. In some examples, the machine learning algorithm is configured to receive, as inputs, the copy number data and the SNP data, and output the respective carrier status of the individual.

Abstract: Capture probe libraries can be used to enrich a region of interest in a sequencing library for high-depth sequencing. The capture probes within the capture probe libraries often do not function in a predictable or uniform manner. Described herein are balanced capture probe libraries and methods of balancing capture probe libraries. A sequencing library can be enriched using balanced capture probe libraries, and the enriched sequencing library can be sequenced to obtain a sequencing depth closer to a desired sequencing depth.

Abstract: High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduces sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are sequencing adapters comprising a nondegenerate or variable length molecular barcode and compositions comprising a plurality of sequencing adapters, which can be useful for sequencing nucleic acids. Further provided are methods of using the sequencing adapters, including methods of sequencing nucleic acids, methods of identifying an error in a nucleic acid sequence, and methods of determining the number of nucleic acid molecules in a library.