JP-2022532403-A5 -

Dates

Publication Date

20230518

Application Date

20200515

Description

In some embodiments of the above methods, sequencing data is obtained by sequencing nucleic acid molecules obtained from multiple individuals in a pooled sample. In some embodiments, the selected loci are unique to each individual among the multiple individuals. In some embodiments, at least one of the selected loci is common to at least two individuals among the multiple individuals. In some embodiments, the sequencing depth is determined for each individual, and the signal for each individual is adjusted based on the sequencing depth associated with that individual. In embodiments of the present invention, for example, the following items are provided. (Item 1) A method for measuring the level of disease in an individual, A step of comparing a signal indicating the rate at which sequenced loci selected from a panel of individualized disease-associated small nucleotide variants (SNVs) originate from affected tissue, using nucleic acid sequencing data associated with the individual, with a background index indicating the sequencing false-positive error rate across the selected loci; and The step of determining the level of disease in the individual based on the comparison of the signal and the background index. A method that includes this. (Item 2) The method according to item 1, wherein the level of the disease is the proportion of nucleic acid molecules related to the disease in a sample from the individual. (Item 3) The method according to item 1 or 2, wherein the comparison step includes subtracting the background index from the signal. (Item 4) The method according to any one of items 1 to 3, further comprising the step of determining an error in measuring the level of the disease. (Item 5) The method according to item 4, wherein the error is a confidence interval for the level of the disease. (Item 6) The method according to item 4 or 5, wherein the error is proportional to the total number of individual small nucleotide variant reads detected at the selected locus. (Item 7) The level of the disease is the proportion of nucleic acid molecules related to the disease in a sample from the individual, and the proportion and error are, (In the formula, F is a ratio, N total is the total number of individual small nucleotide variant reads detected at the selected gene locus. Nvar is the number of selected gene loci. D is the average sequencing depth, E is the false positive error rate across the selected gene loci. The method described in item 6, as defined by [the relevant article]. (Item 8) The method according to any one of items 1 to 7, comprising the step of measuring the recurrence of the disease. (Item 9) The method according to any one of items 1 to 7, comprising the step of measuring the progression or regression of the disease by comparing the measured level of the disease with a previously measured level of the disease. (Item 10) The method according to item 9, wherein the progression or regression of the disease is based on a statistically significant change in the measured level of the disease. (Item 11) A method for detecting diseases in individuals, A step of comparing a signal indicating the rate at which sequenced loci selected from a panel of individualized disease-associated small nucleotide variants (SNVs) originate from affected tissue, using nucleic acid sequencing data associated with the individual, with a noise index indicating the sampling variance across the selected loci; and A step of determining whether the individual has the disease based on the comparison between the signal and the noise figure. A method that includes this. (Item 12) The method according to item 11, wherein if the signal exceeds a predetermined threshold and surpasses the noise figure, the individual is determined to have a recurrence of the disease or a residual level of the disease. (Item 13) The method according to item 11, wherein if the signal exceeds the noise figure by k times or more, the individual is determined to have a recurrence of the disease or a residual level of the disease, and k is approximately 1.5. (Item 14) The method according to item 11, wherein if the signal exceeds the noise figure by k times or more, the individual is determined to have a recurrence of the disease or a residual level of the disease, and k is approximately 3.0. (Item 15) The method according to item 11, wherein if the signal exceeds the noise figure by k times or more, the individual is determined to have a recurrence of the disease or a residual level of the disease, and k is approximately 5.0. (Item 16) The method according to item 11, wherein if the signal exceeds the noise figure by k times or more, the individual is determined to have a recurrence of the disease or a residual level of the disease, and k is approximately 10. (Item 17) The method according to any one of items 11 to 16, comprising the step of detecting a recurrence of the disease. (Item 18) The method according to any one of items 1 to 17, wherein