Methods and materials for detecting gene copy number variants

A method for detecting a gene copy number variant (CNV) in a biological sample having one or more genes, the method comprising:

• a) obtaining a set of probes for next generation sequencing wherein each probe in the set hybridizes a different segment of the one or more genes in the biological sample;
• b) performing next generation sequencing with the set of probes on the biological sample to obtain a sequence read for each probe;
• c) adding the sequence reads from each probe to obtain a total number of sequence reads for the set of probes;
• d) dividing the total number of sequence reads by the number of probes in the set of probes to generate a normalization baseline for a probe;
• e) determining a coverage index for the probe in the set of probes by dividing a number of sequence reads obtained for the probe by the normalization baseline;
• and
• f) generating a p-value for a difference between the coverage index of the probe and a set confidence interval established from a normal range of coverage index, wherein a CNV is detected where the p-value is equal to or less than 10−4.

An electronic computer system, comprising:

• a) one or more processors;
• and
• b) a memory storing one or more programs for execution by the one or more processors, the one or more programs comprising instructions for:
• i) analyzing data obtained from next generation sequencing of a biological sample having one or more genes using a set of probes, wherein the data comprises sequence reads for each probe;
• ii) creating a normalization baseline for a probe;
• iii) generating a coverage index for a probe in the set of probes;
• iv) determining a difference between the coverage index of the probe and a set confidence interval established from a normal range of coverage index, wherein a copy number variant is detected where a p-value for the difference is equal to or less than a set threshold.

A method of treating a patient with a targeted therapy, the method comprising:

• a) determining if a gene copy number variant (CNV) is present in a biological sample obtained from the patient, comprising the steps of:
• i) obtaining a set of probes for next generation sequencing (NGS) wherein each probe in the set hybridizes a different segment of the one or more genes;
• ii) performing next generation sequencing with the set of probes on the biological sample comprising the one or more genes to obtain a sequence read for each probe;
• iii) creating a normalization baseline for a probe;
• iv) generating a coverage index for a probe in the set of probes;
• and
• v) determining a difference between the coverage index of the probe and a set confidence interval established from a normal range of coverage index, wherein a CNV is detected where a p-value for the difference between the coverage index of the probe and the set confidence interval is equal to or less than a set threshold;
• and
• b) administering the targeted therapy to the patient where a CNV is detected in the biological sample.