A computer-implemented method for preparing an oligonucleotide combination used to detect a plurality of target nucleic acid sequences with a target coverage of interest from a pool of oligonucleotides, comprising: (a) preparing the plurality of target nucleic acid sequences; (b) preparing the pool of oligonucleotides to be hybridized with the plurality of target nucleic acid sequences; and (c) selecting from the pool of oligonucleotides a least oligonucleotide combination with the target coverage of interest for the plurality of target nucleic acid sequences; wherein the selection of the least oligonucleotide combination is performed to achieve the following objective formula 1 together with satisfying the following constraint formulas 1 and 2, or the constraint formula 2: Min: ∑ p = 1 a x p wherein Min: represents minimization, x p is a binary variable consisting of a non-selection value ( x non-sel) and a selection value ( x sel) for whether or not an oligonucleotide p is selected, and p is a serial number of the oligonucleotide p ranging from 1 to a; ∑ s = 1 b c s ≥ m × S wherein c s is a binary variable consisting of a non-coverage value ( c non - cov) and a coverage value ( c cov) for whether or not a target nucleic acid sequence s is covered, m is a target coverage of interest with a value of 0 < m < 1, S is the total number of the plurality of target nucleic acid sequences, and s is a serial number of a target nucleic acid sequence s ranging from 1 to b; ∑ p = 1 a y s, p x p ≥ c s for all s wherein y s,p is a binary constant consisting of a non-coverage value ( y non - cov) and a coverage value ( y cov) representing whether or not a target nucleic acid sequence s is covered by an oligonucleotide p; x p is a binary variable for whether or not an oligonucleotide p is selected; c s is a binary variable for whether or not a target nucleic acid sequence s is covered in which c s is a coverage value ( c cov) when the target coverage of interest is 100% and c s is a non-coverage value ( c non - cov) and a coverage value ( c cov) when the target coverage of interest is less than 100%; and for all s represents application to all of target nucleic acid sequences s; and wherein the oligonucleotide included in the pool of oligonucleotides satisfies at least one of the following criteria: (i) a T m value of 35°C to 85°C; (ii) a length of 15-50 nucleotides; (iii) a nucleotide sequence with 30-80% GC content; (iv) when the oligonucleotide forms a homodimer, the ratio of consecutive nucleotides involved in the formation of the homodimer is 65% or less; (v) when the oligonucleotide forms a heterodimer with another oligonucleotide, the ratio of nucleotides involved in the formation of the heterodimer is 70% or less; and (vi) when the oligonucleotide forms a heterodimer with another oligonucleotide, the ratio of consecutive nucleotides involved in the formation of the heterodimer is 65% or less. (a) preparing the plurality of target nucleic acid sequences; (b) preparing the pool of oligonucleotides to be hybridized with the plurality of target nucleic acid sequences; and (c) selecting from the pool of oligonucleotides a least oligonucleotide combination with the target coverage of interest for the plurality of target nucleic acid sequences; wherein the selection of the least oligonucleotide combination is performed to achieve the following objective formula 1 together with satisfying the following constraint formulas 1 and 2, or the constraint formula 2: Min: ∑ p = 1 a x p wherein Min: represents minimization, x p is a binary variable consisting of a non-selection value ( x non-sel) and a selection value ( x sel) for whether or not an oligonucleotide p is selected, and p is a serial number of the oligonucleotide p ranging from 1 to a; ∑ s = 1 b c s ≥ m × S wherein c s is a binary variable consisting of a non-coverage value ( c non - cov) and a coverage value ( c cov) for whether or not a target nucleic acid sequence s is covered, m is a target coverage of interest with a value of 0 < m < 1, S is the total number of the plurality of target nucleic acid sequences, and s is a serial number of a target nucleic acid sequence s ranging from 1 to b; ∑ p = 1 a y s, p x p ≥ c s for all s wherein y s,p is a binary constant consisting of a non-coverage value ( y non - cov) and a coverage value ( y cov) representing whether or not a target nucleic acid sequence s is covered by an oligonucleotide p; x p is a binary variable for whether or not an oligonucleotide p is selected; c s is a binary variable for whether or not a target nucleic acid sequence s is covered in which c s is a coverage value ( c cov) when the target coverage of interest is 100% and c s is a non-coverage value ( c non - cov) and a coverage value ( c cov) when the target coverage of interest is less than 100%; and for all s represents application to all of target nucleic acid sequences s; and wherein the oligonucleotide included in the pool of oligonucleotides satisfies at least one of the following criteria: (i) a T m value of 35°C to 85°C; (ii) a length of 15-50 nucleotides; (iii) a nucleotide sequence with 30-80% GC content; (iv) when the oligonucleotide forms a homodimer, the ratio of consecutive nucleotides involved in the formation of the homodimer is 65% or less; (v) when the oligonucleotide forms a heterodimer with another oligonucleotide, the ratio of nucleotides involved in the formation of the heterodimer is 70% or less; and (vi) when the oligonucleotide forms a heterodimer with another oligonucleotide, the ratio of consecutive nucleotides involved in the formation of the heterodimer is 65% or less.