A computer implemented method for determining the presence or absence of a repeat expansion of a repeat sequence of interest in a test sample comprising nucleic acids, wherein the repeat sequence of interest comprises repeats of a repeat unit of nucleotides, the method comprising: (a) obtaining paired end reads of the test sample, and aligning the paired end reads to a reference sequence comprising the repeat sequence of interest, thereby obtaining aligned reads and unaligned reads, wherein the aligned reads are aligned to a particular location in the reference sequence, and wherein the unaligned reads include reads that cannot be aligned or are poorly aligned to the reference sequence; (b) identifying anchor reads in the paired end reads by identifying aligned reads that are aligned to the repeat sequence of interest or to a location within about 5000bp of the repeat sequence of interest as the anchor reads, and identifying anchored reads in the paired end reads by identifying unaligned reads that are paired with the anchor reads as the anchored reads; and (c) determining if the repeat expansion is likely to be present in the test sample based at least in part on numbers of repeats of the repeat unit in the identified anchored reads, wherein (c) comprises: obtaining the number of identified anchor reads that are high-count reads, wherein the high-count reads comprise reads having more repeats than a threshold value; and comparing the number of high-count reads in the test sample to a call criterion, and wherein the threshold value for high-count reads is about 80% of the maximum number of repeats, which maximum is calculated from the length of the paired end reads and the length of the repeat unit. (a) obtaining paired end reads of the test sample, and aligning the paired end reads to a reference sequence comprising the repeat sequence of interest, thereby obtaining aligned reads and unaligned reads, wherein the aligned reads are aligned to a particular location in the reference sequence, and wherein the unaligned reads include reads that cannot be aligned or are poorly aligned to the reference sequence; (b) identifying anchor reads in the paired end reads by identifying aligned reads that are aligned to the repeat sequence of interest or to a location within about 5000bp of the repeat sequence of interest as the anchor reads, and identifying anchored reads in the paired end reads by identifying unaligned reads that are paired with the anchor reads as the anchored reads; and (c) determining if the repeat expansion is likely to be present in the test sample based at least in part on numbers of repeats of the repeat unit in the identified anchored reads, wherein (c) comprises: obtaining the number of identified anchor reads that are high-count reads, wherein the high-count reads comprise reads having more repeats than a threshold value; and comparing the number of high-count reads in the test sample to a call criterion, and wherein the threshold value for high-count reads is about 80% of the maximum number of repeats, which maximum is calculated from the length of the paired end reads and the length of the repeat unit. obtaining the number of identified anchor reads that are high-count reads, wherein the high-count reads comprise reads having more repeats than a threshold value; and comparing the number of high-count reads in the test sample to a call criterion, and wherein the threshold value for high-count reads is about 80% of the maximum number of repeats, which maximum is calculated from the length of the paired end reads and the length of the repeat unit. <EOS>