# US 8,771,949 B2 · Method of identifying target biomolecule by using probe-binding frequency

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- Number: US 8,771,949 B2
- Document ID: US8771949B2
- Status: Granted
- Kind: B2
- Application number: 13/303,813
- Filed: 2011-11-23
- Published: 2012-08-30
- Granted: 2014-07-08
- Earliest claimed: 2011-02-28
- Assignees: Samsung Electronics Co., Ltd.
- Applicants: Tae-jin Ahn; Su-hyeon Kim; Kyoung-gu Woo
- Inventors: Tae-jin Ahn; Su-hyeon Kim; Kyoung-gu Woo
- Web page: https://patentgrep.com/patent/US8771949B2

## CPC

- G16B 15/00: ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

An efficient and accurate method of identifying a target biomolecule in a sample by using target molecule-probe binding frequencies is disclosed.

## Claims

### Claim 1

A method of identifying a target biomolecule, the method comprising:
detecting the binding of each of N nucleic acid probe molecules to a target biomolecule to generate a target signature, which is defined by the binding frequencies of the individual N nucleic acid probe molecules to the target biomolecule, wherein N≧2 and each nucleic acid probe molecule has a unique configuration element that permits specific binding of the nucleic acid probe molecule to the target molecule, wherein the target biomolecule is a nucleic acid;
comparing the target signature to a reference signature pool, wherein the reference signature pool comprises a reference signature for each of a plurality of reference biomolecules, and each reference signature is defined by the binding frequencies of the individual N nucleic acid probe molecules to a reference biomolecule; and
identifying the target biomolecule as being identical to a reference biomolecule if the binding frequencies of the individual nucleic acid probe molecules in the target signature match those in the reference signature within a predetermined confidence level of about 95% or greater with respect to the N nucleic acid probe molecules,
wherein identifying the target biomolecule further comprises: calculating a binding frequency distance (d) according to Equation (1) below, wherein xi denotes an ith binding frequency of the target signature, and yi denotes an ith binding frequency of each of the reference signatures in the reference signature pool;
d
⁡
(
x
→
,
y
→
)
=
∑
i
=
1
N
⁢
(
x
i
-
y
i
)
2
Equation
⁢
⁢
1
and generating a target-reference distance distribution of binding frequency distance (d) defined by a number of counts with respect to each of the binding frequency distances (d), wherein the target biomolecule is identified as being identical to one of the reference biomolecules having a binding frequency distance (d) that is smaller or equal to a predetermined threshold in the target-reference distance distribution.

### Claim 2 (depends on 1)

The method of claim 1, wherein Equation 1 is replaced with Equation 2 below:
d
⁡
(
x
→
,
y
→
)
=
∑
i
=
1
N
⁢
(
x
i
-
y
i
)
2
N
.
Equation
⁢
⁢
2

### Claim 3 (depends on 1)

The method of claim 1, wherein if there are at least two reference biomolecules with reference signatures having binding frequency distances (d) that are smaller than or equal to the threshold in the target-reference distance distribution, the target biomolecule is determined to be identical to the reference biomolecule with the reference signature having the smallest binding frequency distance (d).

### Claim 4

A method of identifying a target biomolecule, the method comprising:
detecting the binding of each of N nucleic acid probe molecules to a target biomolecule to generate a target signature, which is defined by the binding frequencies of the individual N nucleic acid probe molecules to the target biomolecule, wherein N≧2 and each nucleic acid probe molecule has a unique configuration element that permits specific binding of the nucleic acid probe molecule to the target molecule, wherein the target biomolecule is a nucleic acid;
comparing the target signature to a reference signature pool, wherein the reference signature pool comprises a reference signature for each of a plurality of reference biomolecules, and each reference signature is defined by the binding frequencies of the individual N nucleic acid probe molecules to a reference biomolecule; and
identifying the target biomolecule as being identical to a reference biomolecule if the binding frequencies of the individual nucleic acid probe molecules in the target signature match those in the reference signature within a predetermined confidence level of about 95% or greater with respect to the N nucleic acid probe molecules,
wherein the generating of the target signature comprises repeatedly binding each of the N nucleic acid probe molecules to the target biomolecule; and calculating an average binding frequency of each of the N nucleic acid probe molecules with respect to the target biomolecule, thereby generating a target signature, which is defined by the average binding frequencies of the individual N nucleic acid probe molecules, and
the identifying of the target biomolecule further comprises: calculating a binding frequency distance (d) according to Equation (3) below, wherein xi denotes an ith average binding frequency of the target signature, yi denotes an ith binding frequency of each of the reference signatures in the reference signature pool, and σi denotes a standard deviation of the ith average binding frequency of the target signature;
d
⁡
(
x
→
,
y
→
)
=
∑
i
=
1
N
⁢
(
x
i
-
y
i
)
2
σ
i
2
Equation
⁢
⁢
3
and generating a target-reference distance distribution of binding frequency distance (d) defined by a number of counts with respect to each of the binding frequency distances (d), wherein the target biomolecule is identified as being identical to one of the reference biomolecules with a binding frequency distance (d) that is smaller or equal to a predetermined threshold in the target-reference distance distribution.

### Claim 5 (depends on 4)

The method of claim 4, wherein Equation 3 is replaced with Equation 4 below:
d
⁡
(
x
→
,
y
→
)
=
∑
i
=
1
N
⁢
(
x
i
-
y
i
)
2
σ
i
2
N
.
Equation
⁢
⁢
4

### Claim 6 (depends on 4)

The method of claim 4, wherein if there are at least two reference biomolecules with reference signatures having binding frequency distances (d) that are smaller than or equal to the threshold in the target-reference distance distribution, the target biomolecule is determined to be identical to the reference biomolecule with the reference signature having the smallest binding frequency distance (d).