Systems and methods for identifying exon junctions from single reads

A method for identifying a fusion junction in a human transcriptome suspected of containing a gene fusion, the method comprising:

• preparing a fragment library from nucleic acids isolated from the human transcriptome;
• providing a plurality of nucleic acid fragments of the fragment library to a sequencing instrument;
• detecting a plurality of signals, at least some of which are representative of a first sequence of one of the nucleic acid fragments of the fragment library;
• and
• using a processor to:
• generate a first read sequence representative of a first nucleic acid fragment from the plurality of signals,
• generate a list of exon prefix sequences by comparing exons of a human genome to the first read sequence and identifying the exons that have a prefix sequence mapping to a suffix sequence of the first read sequence,
• generate a list of exon suffix sequences by comparing exons of the human genome to the first read sequence and identifying the exons that have a suffix sequence mapping to a prefix sequence of the first read sequence,
• select a pair of exon sequences from the lists of exon prefix sequences and exon suffix sequences, a first exon sequence of the pair being one of the exon suffix sequences and a second exon sequence of the pair being one of the exon prefix sequences,
• calculate a sum of a number of sequence elements of the first exon sequence that overlap the prefix of the first read sequence, a number of sequence elements of the second exon sequence that overlap the suffix of the first read sequence, and a constant,
• if the sum equals a length of the first read sequence, identify a fusion junction between exons associated with the first exon sequence and second exon sequence in the human transcriptome using the processor, and identify a presence of a gene fusion in the human transcriptome based on the identified fusion junction, and
• if the sum does not equal a length of the first read sequence, repeat the selecting of a pair of exon sequences and calculating of the sum for a different pair of exon sequences from the lists of exon prefix sequences and exon suffix sequences.

A computer program product, comprising a non-transitory computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for identifying a fusion junction in a human transcriptome suspected of containing a gene fusion, the instructions comprising:

• instructions to receive a plurality of nucleic acid fragments of a fragment library, the fragment library comprising nucleic acid fragments created from the human transcriptome, into a sequencing instrument;
• instructions to provide reagents for sequencing the nucleic acid fragments;
• instructions to detect a plurality of signals during sequencing, at least a portion of the signals representative of a sequence of at least one of the nucleic acid fragments;
• instructions to determine a first read sequence representative of the at least one nucleic acid fragment using the plurality of signals;
• instructions to generate a list of exon prefix sequences by comparing exons of a human genome to the first read sequence and identifying the exons that have a prefix sequence mapping to a suffix sequence of the first read sequence,
• instructions to generate a list of exon suffix sequences by comparing exons of the human genome to the first read sequence and identifying the exons that have a suffix sequence mapping to a prefix sequence of the first read sequence,
• instructions to store the list of exon prefix sequences and the list of exon suffix sequences;
• instructions to select a pair of exon sequences from the stored lists of exon prefix sequences and exon suffix sequences, a first exon sequence of the pair being one of the exon suffix sequences and a second exon sequence of the pair being one of the exon prefix sequences;
• instructions to calculate a sum of a number of sequence elements of the first exon sequence that overlap the prefix of the first read sequence, a number of sequence elements of the second exon sequence that overlap the suffix of the first read sequence, and a constant;
• instructions to identify a fusion junction between exons associated with the first exon sequence and second exon sequence when the sum equals a length of the first read sequence, and to identify a presence of a gene fusion in the human transcriptome based on the identified fusion junction;
• and
• instructions to repeat the selecting of a pair of exon sequences and calculating of the sum for a different pair of exon sequences from the stored lists of exon prefix sequences and exon suffix sequences when the sum does not equal a length of the first read sequence.