Methods, systems and processes of identifying genetic variations

Abstract

Provided herein are novel methods, systems and processes for generating and analyzing sequence data for the determination of the presence or absence of one or more genetic variations within a genome of a subject.

1 - 20 . (canceled) 
     
     
         21 . A method of genome analysis comprising:
 a) obtaining sequence reads from a sample obtained from a human subject having or suspected of having a disease or condition associated with a genetic variation, wherein
 (i) the reads are generated using a targeted approach, 
 (ii) the reads represent less than 10% of the entire genome of the subject, 
 (iii) the average distance between the reads is at least 4000 bp, 
 (iv) the reads comprise sequence information for at least 100,000 polymorphisms, and 
 (v) each read comprises sequence information for at least one of the at least 100,000 polymorphisms; and 
   b) determining an allele balance for one or more of the at least 100,000 polymorphisms.   
     
     
         22 . The method of claim  1 , wherein one or more, or all of the at least 100,000 polymorphisms comprise single nucleotide polymorphisms (SNPs). 
     
     
         23 . The method of claim  1 , wherein an allele balance is determined for substantially all of the at least 100,000 polymorphisms. 
     
     
         24 . The method of claim  1 , further comprising, after (b), determining a presence or absence of heterozygosity for a portion of the subject's genome comprising at least one of the at least 100,000 polymorphisms. 
     
     
         25 . The method of claim  4 , wherein the determining of the presence or absence of heterozygosity is determined according to the allele balance determined in (b). 
     
     
         26 . The method of claim  4 , further comprising determining a presence or absence of a copy number variation (CNV) for the portion of the subject's genome according to the presence or absence of heterozygosity. 
     
     
         27 . The method of claim  6 , wherein the presence or absence of the copy number variation is determined by a process comprising a Hidden Markov Model or Viterbi algorithm statistical model, maximum likelihood regression, a negative binomial statistical model of the read-counts, or Expectation-Maximization. 
     
     
         28 . The method of claim  1 , wherein the sequence information comprises a haplotype for an allele of the subject's genome for one or more of the polymorphisms. 
     
     
         29 . The method of claim  1 , wherein the reads represent less than 5% of the entire genome of the subject. 
     
     
         30 . The method of claim  1 , wherein the reads comprise single end reads. 
     
     
         31 . The method of claim  10 , wherein the single-end reads are obtained by a process comprising a next generation sequencing (NGS) method, and are generated in a single sequencing run or from a single flow cell. 
     
     
         32 . The method of claim  1 , wherein the reads are generated from at least 100,000 different targeted primers. 
     
     
         33 . The method of claim  1 , wherein each of the reads is between about 50 and about 200 nucleotides in length. 
     
     
         34 . The method of claim  1 , wherein an AOH score is determined for substantially all of the polymorphisms. 
     
     
         35 . The method of claim  1 , wherein the sample comprises blood or a blood product obtained from the subject. 
     
     
         36 . The method of claim  1 , wherein the sample comprises cancer cells. 
     
     
         37 . The method of claim  1 , wherein the sample comprises a mixture of nucleic acids comprising two or more nucleic acid species having different origins. 
     
     
         38 . The method of claim  17 , wherein one of the two or more nucleic acid species comprises a gene comprising the genetic variation. 
     
     
         39 . The method of claim  1 , wherein the sample comprises cell-free nucleic acids. 
     
     
         40 . The method of claim  1 , further comprising determining an allele frequency for one or more of the at least 100,000 polymorphisms.