Abstract: The present disclosure provides methods for sequencing and analysis of nucleic acids.

Abstract: 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 (CNV) 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, such as a size-weighted coverage or a fraction of fragments in a size range. In some embodiments, the fragment size parameter is adjusted to remove within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples.

Abstract: The present disclosure provides methods for diagnosis of interstitial lung diseases (ILDs). The present disclosure provides methods for differential diagnosis of idiopathic pulmonary fibrosis from other ILDs. Compositions and kits useful in carrying out a subject method are also provided.

Abstract: The disclosure relates to computer technology for precision diagnosis of various states of genetic material such as a gene sequenced from cell-free DNA in a sample. The state may include a somatic homozygous deletion, a somatic heterozygous deletion, a copy number variation, or other states. A computer system may generate competing probabilistic models that each output a probability that the genetic material is in a certain state. Each model may be trained on a training sample set to output a probability that the genetic material is in a respective state. In some embodiments, the computer system may use various probabilistic distributions to generate the models. For example, the computer system may use a beta-binomial distribution, a binomial distribution, a normal (also referred to as “Gaussian”) distribution, or other type of probabilistic modeling techniques.

Abstract: A system and a method are described for applying a noise model for predicting the occurrence and a level of noise that is present in cfDNA read information. The significance model is trained for a plurality of stratifications of called variants using training data in the stratification. Stratifications may include a partition and a mutation type. The significance model predicts the likelihood of observing a read frequency for a called variant in view of two distributions of the significance model. The first distribution predicts a likelihood of noise occurrence in the sample. The second distribution predicts a likelihood of observing a magnitude of the read frequency for the called variant. The two distributions may further depend on a baseline noise level of blank samples. With these two distributions, the significance model, for a particular stratification, more accurately predicts the likelihood of a false positive for a called variant.

Abstract: 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.

Abstract: 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.

Abstract: Cross-contamination of a test sample used to determine cancer is identified using gene sequencing data. Each test sample includes a number of test sequences that may include a single nucleotide polymorphism (SNP) that can be indicative of cancer. The test sequences are be filtered to remove or negate at least some of the SNPs from the test sequences. Negating the test sequences allows more test sequences to be simultaneously analyzed to determine cross-contamination. Cross-contamination is determined by modeling the variant allele frequency for the test sequences as a function of minor allele frequency, contamination level, and background noise. In some cases, the variant allele frequency is based on a probability function including the minor allele frequency. Cross-contamination of the test sample is determined if the determined contamination level is above a threshold and statistically significant.

Abstract: Gene copy number variations are identified for genes in a targeted gene panel. For each gene, coverage at each base position across the gene is determined. The coverage at each base position can be influenced by the hybridization probes that are used to determine the base level coverage of the base position. The base level coverage for each base position is normalized to account for the characteristics of the hybridization probes. To determine whether a copy number variation exists for a gene, the base level coverage of base positions across the gene for a subject is analyzed to determine whether it deviates from the base level coverage of base positions across the gene for previously analyzed, healthy individuals. If a significant deviation exists, a copy number variation for the gene is called.

Abstract: 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 (CNV) 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, such as a size-weighted coverage or a fraction of fragments in a size range. In some embodiments, the fragment size parameter is adjusted to remove within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples.

Abstract: The present disclosure provides methods for diagnosis of interstitial lung diseases (ILDs). The present disclosure provides methods for differential diagnosis of idiopathic pulmonary fibrosis from other ILDs. Compositions and kits useful in carrying out a subject method are also provided.

Abstract: 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.

Abstract: Methods for the determination of a copy number of a target genomic sequence; either a target gene or genomic sequence of interest, in a biological sample are described. Various methods utilize a model drawn from a probability density function (PDF) for the assignment of a copy number of a target genomic sequence in a biological sample. Additionally, the methods provide for the determination of a confidence value for a copy number assigned to a sample based on attributes of the sample data. Accordingly, the various methods for the determination of a copy number provide the end user with significant information for the evaluation of a copy number of a target genomic sequence; either a gene or genomic sequence of interest.

Abstract: Disclosed herein are kits, compositions, and methods relating to the classification of samples. Methods disclosed herein can also be used to diagnose conditions or to support treatment-related decisions.

Abstract: The present disclosure provides methods for diagnosis of interstitial lung diseases (ILDs). The present disclosure provides methods for differential diagnosis of idiopathic pulmonary fibrosis from other ILDs. Compositions and kits useful in carrying out a subject method are also provided.

Abstract: We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status, and carried out a comprehensive gene expression survey on peripheral blood cells obtained from TAA patients and normal individuals. A distinct gene expression profile in peripheral blood cells can classify TAA patients from normal individuals. The genes provided by the present teachings define a set of diagnostic markers, thus providing a blood-based gene expression test to facilitate early detection of TAA disease. Methods of distinguishing ascending from descending TAA are also provided, as are methods of distinguishing familial from sporadic TAA.

Abstract: Methods for the determination of a copy number of a target genomic sequence; either a target gene or genomic sequence of interest, in a biological sample are described. Various methods utilize a model drawn from a probability density function (PDF) for the assignment of a copy number of a target genomic sequence in a biological sample. Additionally, the methods provide for the determination of a confidence value for a copy number assigned to a sample based on attributes of the sample data. Accordingly, the various methods for the determination of a copy number provide the end user with significant information for the evaluation of a copy number of a target genomic sequence; either a gene or genomic sequence of interest.

Abstract: We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status, and carried out a comprehensive gene expression survey on peripheral blood cells obtained from TAA patients and normal individuals. A distinct gene expression profile in peripheral blood cells can classify TAA patients from normal individuals. The genes provided by the present teachings define a set of diagnostic markers, thus providing a blood-based gene expression test to facilitate early detection of TAA disease. Methods of distinguishing ascending from descending TAA are also provided, as are methods of distinguishing familial from sporadic TAA.