CN-121978168-A - DNA damage base detection method, system and terminal based on molecular conductance

Abstract

The invention relates to the technical field of DNA adduct detection, in particular to a DNA damage base detection method, a system and a terminal based on molecular conductivity, wherein the detection method comprises the steps of controlling an electrode gap between two metal electrodes modified with recognition probes, and enabling the recognition probes and the DNA adduct to form a single molecular junction; and inputting the current signal into a trained DNA damage base detection model, and outputting a detection result of the DNA adduct. Molecular recognition is carried out by utilizing the DNA adducts and recognition probes on the two metal electrodes through hydrogen bond pairing so as to form a single molecular junction with a sandwich structure, electrons pass through the single molecular junction to generate tunneling current signals under the drive of constant bias voltage, and the detection result of the DNA adducts corresponding to the current signals can be obtained based on a trained DNA damage base detection model. The detection method can realize higher spatial resolution and is favorable for identifying DNA damaged bases with similar structures.

Inventors

• ZHANG BINTIAN
• LIU YULU
• SHI SANJUN

Assignees

• 南方科技大学

Dates

Publication Date

20260505

Application Date

20251211

Claims (10)

1. 1. A method for detecting a DNA damage base based on molecular conductance, which is characterized by comprising the following steps: controlling an electrode gap between two metal electrodes modified with recognition probes, and enabling the recognition probes and DNA adducts to form a single-molecule junction; applying a constant bias voltage to the metal electrode to acquire a current signal of the single-molecule junction; inputting the current signal into a trained DNA damage base detection model, and outputting a detection result of the DNA adduct.
2. 2. The method for detecting a DNA damage base based on molecular conductance according to claim 1, wherein the recognition probe comprises at least one of thiolated benzamide, imidazole-carboxamide derivative.
3. 3. The method for detecting a DNA damage base based on molecular conductance according to claim 1, wherein the electrode gap is 1nm to 5nm.
4. 4. The method for detecting a DNA damage base based on molecular conductance according to claim 1, wherein the constant bias is-0.2V to-0.5V.
5. 5. The method for detecting a DNA damage base based on molecular conductance according to claim 1, wherein the training of the trained DNA damage base detection model comprises the steps of: Controlling an electrode gap between two metal electrodes modified with recognition probes, and enabling the recognition probes to form different single-molecule junctions with different DNA adducts; applying a constant bias voltage to the metal electrode to obtain a current signal of the single-molecule junction, and preprocessing to obtain a signal cluster; And inputting the signal clusters into a machine learning model for training to obtain a DNA damage base detection model.
6. 6. The method for detecting a DNA damage base based on molecular conductance according to claim 5, wherein the pretreatment comprises the steps of: Converting the current signal into a digital signal, and carrying out noise elimination processing on the digital signal by using a wiener filter function; Convolving the digital signal subjected to noise cancellation by using a Gaussian window with the width of a preset data point, and identifying the convolved continuous higher than the preset data point as a signal cluster; Extracting a time domain signal of the signal cluster, converting the time domain signal into a frequency domain signal and a cepstral domain signal after Fourier transformation and 1/f noise elimination, and respectively downsampling the frequency domain signal and the cepstral domain signal into a plurality of signal intervals to obtain frequency domain signal characteristics and cepstral domain signal characteristics; Based on the frequency domain signal characteristics and the cepstral domain signal characteristics, core characteristics capable of distinguishing different bases or adducts are screened out by utilizing a mutual information algorithm and used as single base signal clusters or single adduct signal clusters.
7. 7. The method of detecting a DNA damage base based on molecular conductance according to claim 6, wherein the time domain signal comprises a signal cluster time domain width, a number of peaks in a signal cluster, a signal cluster maximum peak height, a signal cluster minimum peak height, an average peak width, an average peak height, a signal cluster maximum current value, a signal cluster minimum current value.
8. 8. A DNA damage base detection system based on molecular conductance, comprising: A reaction module for controlling an electrode gap between two metal electrodes modified with recognition probes and forming a single-molecule junction between the recognition probes and the DNA adducts; The data acquisition module is used for applying a constant bias voltage to the metal electrode and acquiring a current signal of the single-molecule junction; and the result output module is used for inputting the current signal into a trained DNA damage base detection model and outputting a detection result of the DNA adduct.
9. 9. A terminal comprising a memory, a processor, and a program stored on the memory and executable on the processor, which when executed by the processor, performs the steps of the molecular conductivity-based DNA damage base detection method of any one of claims 1 to 7.
10. 10. A computer-readable storage medium, having stored thereon a computer program, the computer-readable storage medium having stored thereon a molecular conductance-based DNA damage base detection program, which when executed by a processor, implements the steps of the molecular conductance-based DNA damage base detection method of any one of claims 1-7.

Description

DNA damage base detection method, system and terminal based on molecular conductance Technical Field The invention relates to the technical field of DNA adduct detection, in particular to a DNA damage base detection method, system and terminal based on molecular conductivity. Background Exogenous factors such as ionizing radiation, ultraviolet irradiation, mutagenic chemicals and the like can damage DNA to different degrees, damage the stability of the structure of the DNA and influence the accurate expression of the DNA, so that certain toxicity is generated on cells, the risk of gene mutation of the cells is increased, and particularly the occurrence risk of diseases such as cancers and the like is increased. Currently, DNA adducts are important indicators of great interest in cancer diagnosis, accurate medicine, toxicity assessment and epidemic investigation as sensitive biomarkers, however, because of the wide variety, similar structure and extremely low content of DNA adducts, accurate quantitative analysis of adducts is very challenging and also becomes a bottleneck breaking through for related field study. The traditional DNA adduct detection method mainly comprises 32 P post-labeling method, high performance liquid chromatography-mass spectrometry (HPLC-MS), immunoassay method, electrochemical sensing method and the like, and the wide application of the methods is mainly attributed to detection sensitivity and accuracy. However, these methods have drawbacks such as extremely high sensitivity of 32 P post-labeling, potential health risks to the experimenters due to the radioisotope labeling procedure required, and failure to provide structural information of the base adducts to the detection results. The mass spectrometry technology relies on expensive instruments and has the characteristics of high use cost, complex operation, long analysis period and the like. Immunoassays lack versatility and are susceptible to detection of false positives due to structural similarity of DNA adducts. Electrochemical sensors are based on the electrochemical signal of the base and therefore lack sensitivity to changes in the structure of the adducts, resulting in poor selectivity of this type of technology. Accordingly, the prior art is still in need of improvement and development. Disclosure of Invention In view of the above-mentioned shortcomings of the prior art, the present invention aims to provide a method, a system and a terminal for detecting DNA damaged bases based on molecular conductance, which aims to solve the problems that the existing DNA damaged base detection method has poor selectivity on adducts and can not provide structural information of the base adducts. The technical scheme of the invention is as follows: A DNA damage base detection method based on molecular conductance comprises the following steps: controlling an electrode gap between two metal electrodes modified with recognition probes, and enabling the recognition probes and DNA adducts to form a single-molecule junction; applying a constant bias voltage to the metal electrode to acquire a current signal of the single-molecule junction; inputting the current signal into a trained DNA damage base detection model, and outputting a detection result of the DNA adduct. The DNA damage base detection method based on molecular conductivity, wherein the recognition probe comprises at least one of sulfhydryl benzamide, imidazole-formamide and imidazole-formamide derivatives. The DNA damage base detection method based on molecular conductivity, wherein the electrode gap is 1nm-5nm. The DNA damage base detection method based on molecular conductance, wherein the constant bias voltage is-0.2V to-0.5V. The molecular conductivity-based DNA damage base detection method, wherein the training of the trained DNA damage base detection model comprises the following steps: Controlling an electrode gap between two metal electrodes modified with recognition probes, and enabling the recognition probes to form different single-molecule junctions with different DNA adducts; applying a constant bias voltage to the metal electrode to obtain a current signal of the single-molecule junction, and preprocessing to obtain a signal cluster; And inputting the signal clusters into a machine learning model for training to obtain a DNA damage base detection model. The DNA damage base detection method based on molecular conductivity, wherein the pretreatment comprises the following steps: Converting the current signal into a digital signal, and carrying out noise elimination processing on the digital signal by using a wiener filter function; Convolving the digital signal subjected to noise cancellation by using a Gaussian window with the width of a preset data point, and identifying the convolved continuous higher than the preset data point as a signal cluster; Extracting a time domain signal of the signal cluster, converting the time domain signal into a frequency domain sign