Verinata Health, Inc.

Echelon Diagnostics, Inc.

Biotique Systems, Inc.

John P Burke

Brian K Rhees

Richard P Rava

Stephen Healy Sanders

Hui Huang

Erich D Blume

Michael Rogoff

Techniques for measuring abundances of sequences includes obtaining first data that indicates a target sequence at a plurality of loci, wherein the target sequence comprises a plurality of bins of loci for which a relative abundance is indicative of a condition of interest. Second data is determined that indicates alignment with the target sequence of reads of DNA fragments in a sample from the subject. Third data is determined that indicates locus dependent observed variations in abundance. A raw count Hj of reads is determined that start at each locus j; and, a copy number of a first bin is determined based on a sum over all loci in the first bin of expected counts for each partition weighted by the locus dependent observed variations. Output data that indicates condition of the subject based at least in part on the copy number of the first bin is presented.

System for increasing the accuracy of non invasive prenatal diagnostics and liquid biopsy by observed loci bias correction at single base resolution

A method and apparatus for automatically determining a characteristic of a crop using an unmanned aerial vehicle (UAV) includes operating the UAV at an elevation above a ground surface of a field and collecting first data that indicates an elevation of the UAV with a barometric pressure based altimeter of the UAV. Second data is collected with a SONAR sensor of the UAV that indicates a distance to a nearest object on the ground surface. The SONAR sensor has a SONAR sensor range and the elevation above the ground surface is less than the SONAR sensor range. The method further includes receiving the first data and the second data on a processor, and determining a height of the nearest object above the ground surface with the processor based on the first data and second data. Output data that indicates the height of the nearest object is presented on a display.

System and method for automatically determining crop characteristics using unmanned aerial vehicle (UAV)

Disclosed are methods and tools for rapidly aligning reads to a reference sequence. These methods and tools employ Bloom filters or similar set membership testers to perform the alignment. The reads may be short sequences of nucleic acids or other biological molecules and the reference sequences may be sequences of genomes, chromosomes, etc. The Bloom filters include a collection of hash functions, a bit array, and associated logic for applying reads to the filter. Each filter, and there may be multiple of these used in a particular application, is used to determine whether an applied read is present in a reference sequence. Each Bloom filter is associated with a single reference sequence such as the sequence of a particular chromosome. In one example, chromosomal abundance is determined by aligning reads from a sequencer to multiple chromosomes, each having an associated Bloom filter or other set membership tester.

Set membership testers for aligning nucleic acid samples

Techniques for automated determination or correction of count bias are based on nucleic acid base content on a finer grained scale than a bin of interest in a target sequence. The techniques include obtaining a target sequence with bins where relative abundances indicate a condition and raw counts Hj of reads, from a subject, which start at each locus j. A partition indicates a fine-grained window at a position relative to a current locus and multiple strata indicating different base contents. Each locus is attributed to one stratum k(j). An expected count of each stratum, E(k), is determined based on Hj for j belonging to the stratum and a number of loci in the target belonging to the stratum. A copy number of a bin is based on a sum of E(k(j)) in the bin. Output data indicates condition of the subject based at least partly on the copy number.

Techniques for fine grained correction of count bias in massively parallel DNA sequencing

Methods of reliably estimating genomic fraction (e.g., fetal fraction) from polymorphisms such as small base variations or insertions-deletions are disclosed. Sequenced data from a multigenomic source is used to determine allele counts for one or more of the polymorphisms. For one or more of the polymorphisms, zygosity is assigned, and genomic fraction is determined from the zygosity and allele counts. Certain embodiments employ SNPs as the relevant polymorphism. The disclosed methods can be applied as part of an intentional, pre-designed re-sequencing study targeted against known polymorphisms or can be used in a retrospective analysis of variations found by coincidence in overlapping sequences generated from maternal plasma (or any other setting where a mixture of DNA from several people are present).

Resolving genome fractions using polymorphism counts

Techniques for construction of internal controls for improved accuracy and sensitivity of DNA testing include obtaining first data and determining weights over real numbers for a normalization function in less than a day. The first data indicates a measured amount of reference sequences for nucleic acids from training samples. The reference sequences include a target, for which an abundance is indicative of a condition of interest, and covariates not correlated with the condition of interest. The normalization function involves a sum of abundances of the covariates, as internal controls, each multiplied by a corresponding one of the weights. The weights are determined based on minimizing variance of a Taylor expansion of a ratio of a measured amount of the target divided by a value of the normalization function evaluated with measured amounts of the covariates over a portion of the first data in which the condition is absent.

System and method for construction of internal controls for improved accuracy and sensitivity of DNA testing

Methods are disclosed for resolving measurement problems such problems in measuring chromosomal copy number. Some disclosed methods involve first selecting a primary assay element characteristic to partition. Such characteristic may be a source of experimental variability such as the GC content of measured DNA sequences. Additionally, the disclosed methods may employ an abundance or copy number function to transform the assay element frequencies into an abundance, dose, copy number score, or the like. In some cases, the disclosed methods estimate an amount of certain fetal DNA in a sample. The methods can further compare the estimated amount to a measured amount of fetal DNA in the sample. The comparison can be used to determine the fetal sex or aneuploidy.

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Reno, NV, United States of America

John P Burke