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CN-122000023-A - Neonatal genetic disease gene and metabolite combined screening method, system and equipment

CN122000023ACN 122000023 ACN122000023 ACN 122000023ACN-122000023-A

Abstract

The invention relates to a method, a system and equipment for screening a neonate genetic disease gene and a metabolite in a combined way, wherein the method comprises the steps of rapidly detecting a neonate biological sample for a plurality of metabolites to obtain metabolic spectrogram data, comparing the metabolic spectrogram data with a metabolic phenotype-genotype association knowledge base, automatically identifying an abnormal metabolic phenotype meeting preset conditions, automatically triggering gene analysis of a specific gene corresponding to a target genetic disease in the same biological sample in response to the identified abnormal metabolic phenotype, and generating a combined screening report based on the abnormal metabolic phenotype and the gene analysis result of the specific gene so as to achieve the purpose of accurately and efficiently tracing from a nonspecific metabolic disorder index to a specific pathogenic gene root source and providing an integrated screening and auxiliary diagnosis solution method for the neonate genetic disease.

Inventors

  • WU LIPING
  • Hui Yufan
  • YANG JIANGTAO

Assignees

  • 深圳爱湾医学检验实验室

Dates

Publication Date
20260508
Application Date
20251231

Claims (10)

  1. 1. A method for screening neonatal genetic disease genes and metabolites in combination, comprising the steps of: Carrying out rapid detection on a neonate biological sample for a plurality of metabolites to obtain metabolic profile data, wherein the metabolic profile data comprises quantitative information of a plurality of small molecule metabolites; Comparing the metabolic spectrogram data with a metabolic phenotype-genotype association knowledge base, and automatically identifying an abnormal metabolic phenotype meeting preset conditions, wherein the abnormal metabolic phenotype is associated with at least one target genetic disease; Automatically triggering a genetic analysis of a specific gene in the same biological sample corresponding to the genetic disorder of interest in response to the identified abnormal metabolic phenotype; Based on the abnormal metabolic phenotype and the results of the genetic analysis of the specific gene, a joint screening report is generated.
  2. 2. The method for combined screening of genes and metabolites of a neonatal genetic disease according to claim 1, wherein said step of rapidly detecting a plurality of metabolites in a neonatal biological sample to obtain metabolic profile data comprises: Synchronously scanning and quantitatively analyzing amino acid and organic acid spectra in a biological sample of the newborn by a mass spectrometer, wherein the biological sample of the newborn is a dry blood spot sample; metabolic profile data is obtained that contains quantitative information for a variety of small molecule metabolites.
  3. 3. The method for combined screening of genes and metabolites of a neonatal genetic disease according to claim 1, wherein said step of automatically identifying abnormal metabolic phenotypes meeting preset conditions by comparing said metabolic profile data with a metabolic phenotype-genotype correlation knowledge base comprises: comparing the specific metabolite concentration in the metabolic spectrogram data with a reference concentration range in a pre-constructed metabolic phenotype-genotype correlation knowledge base; Mapping candidate target genetic diseases from a metabolic phenotype-genotype association knowledge base based on a combined pattern of one or more specific metabolites when the concentration of the one or more specific metabolites is identified as continuously deviating from a corresponding reference concentration range; Calculating the associated confidence of each candidate target genetic disease; Only if the association confidence exceeds a preset threshold, determining an abnormal metabolic phenotype associated with the genetic disorder of interest.
  4. 4. The method for combined screening of neonatal genetic disease genes and metabolites according to claim 3, wherein said construction step of metabolic phenotype-genotype association knowledge base comprises: Obtaining metabolic spectrogram data and gene sequencing results from clinically definite genetic disease cases to form a training data set; Extracting characteristics of the metabolic spectrogram data in the training data set, and determining one or more marked metabolites and a reference concentration range related to a specific genetic disease; establishing a mapping relationship between the abnormal combination pattern of the one or more marker metabolites and the corresponding pathogenic genes; Based on the mapping, a metabolic phenotype-genotype association knowledge base for automatic identification and trigger verification is generated and stored.
  5. 5. The neonatal genetic disease gene and metabolite combination screening method of claim 1, wherein the step of automatically triggering gene analysis of a specific gene corresponding to the genetic disease of interest in the same biological sample in response to the identified abnormal metabolic phenotype comprises: Querying and determining one or more specific genes to be analyzed from the metabolic phenotype-genotype correlation knowledge base based on the identified abnormal metabolic phenotype; automatically generating an analysis instruction containing the specific gene identification, and starting gene analysis on the same neonatal biological sample.
  6. 6. The method for combined screening of neonatal genetic disease genes and metabolites according to claim 1, wherein said step of generating a combined screening report based on the results of the abnormal metabolic phenotype and the gene analysis of the specific gene, comprises: carrying out weighted fusion calculation on the metabolic disorder risk indicated by the abnormal metabolic phenotype and the gene defect risk indicated by the gene analysis result of the specific gene; Determining a final comprehensive risk assessment level according to the weighted fusion calculation result; Generating a joint screening report comprising the abnormal metabolic phenotype, the gene analysis result and the comprehensive risk assessment grade.
  7. 7. The neonatal genetic disease gene and metabolite combination screening method of claim 1 or 6, wherein the step of generating a combination screening report further comprises: carrying out logic consistency check on the abnormal metabolic phenotype and the gene analysis result of the specific gene; Generating a final definitive diagnosis or high risk cue when the verification result indicates that the metabolic phenotype and the genotype conclusion support each other; when the checking result indicates that the metabolic phenotype and the genotype conclusion are contradictory, a prompt message for suggesting review or further differential diagnosis is generated in the combined screening report.
  8. 8. A neonatal genetic disease gene and metabolite combination screening system comprising: the metabolism detection module is used for rapidly detecting various metabolites of the neonatal biological sample to obtain metabolism spectrogram data, wherein the metabolism spectrogram data comprises quantitative information of various small molecule metabolites; the abnormal identification module is used for comparing the metabolic spectrogram data with a metabolic phenotype-genotype association knowledge base and automatically identifying an abnormal metabolic phenotype which meets preset conditions, wherein the abnormal metabolic phenotype is associated with at least one target genetic disease; The gene triggering module is used for responding to the identified abnormal metabolic phenotype and automatically triggering the gene analysis of the specific genes corresponding to the target genetic disease in the same biological sample; and the report generation module is used for generating a combined screening report based on the abnormal metabolic phenotype and the gene analysis result of the specific gene.
  9. 9. A computer device comprising a memory and a processor, the memory having stored therein a computer program, characterized in that the processor, when executing the computer program, carries out the steps of the neonatal genetic disease gene and metabolite combination screening method of any one of claims 1 to 7.
  10. 10. A computer readable storage medium having stored thereon a computer program, characterized in that the computer program when executed by a processor implements the steps of the neonatal genetic disease gene and metabolite combination screening method of any of claims 1 to 7.

Description

Neonatal genetic disease gene and metabolite combined screening method, system and equipment Technical Field The invention relates to the technical field of biomedical detection, in particular to a method, a system and equipment for screening neonatal genetic disease genes and metabolites in a combined way. Background Currently, the mainstream screening strategies for neonatal genetic disease screening rely mostly on tandem mass spectrometry for metabolite screening or gene analysis based on gene chip/sequencing. These two paths tend to be independent of each other in practice, with significant limitations. The metabolite screening can effectively reflect the current physiological disorder of organisms, but the result is easily interfered by non-genetic factors, the false positive rate is high, the root cause of the pathogenicity cannot be revealed, while the extensive gene screening can directly detect the gene defect, but has high cost, complex data interpretation, difficult distinction of clinically significant variation and is not suitable for the primary screening of large-scale people. The separation of metabolism and gene detection leads to the splitting of a screening process, when abnormal metabolic indexes are found, a clinician is often required to manually determine whether and how to carry out gene verification by experience, the whole process is low in efficiency and long in period, and partial infants, especially rare infants with complicated clinical manifestations, are very easy to be missed due to the omission caused by artificial judgment. Disclosure of Invention The invention mainly aims to provide a method, a system and equipment for screening neonatal genetic diseases by combining metabolic phenotype and metabolite, and aims to realize accurate and efficient tracing from nonspecific metabolic disorder indexes to specific pathogenic gene sources and provide an integrated screening and auxiliary diagnosis solution for the neonatal genetic diseases by constructing an automatic association and verification closed loop of metabolic phenotype and genotype. In order to achieve the above object, the present invention provides a method for screening a neonatal genetic disease gene in combination with a metabolite, comprising the steps of: Carrying out rapid detection on a neonate biological sample for a plurality of metabolites to obtain metabolic profile data, wherein the metabolic profile data comprises quantitative information of a plurality of small molecule metabolites; Comparing the metabolic spectrogram data with a metabolic phenotype-genotype association knowledge base, and automatically identifying an abnormal metabolic phenotype meeting preset conditions, wherein the abnormal metabolic phenotype is associated with at least one target genetic disease; Automatically triggering a genetic analysis of a specific gene in the same biological sample corresponding to the genetic disorder of interest in response to the identified abnormal metabolic phenotype; Based on the abnormal metabolic phenotype and the results of the genetic analysis of the specific gene, a joint screening report is generated. Further, the steps of rapidly detecting a plurality of metabolites in the neonatal biological sample to obtain the metabolic profile data comprise: Synchronously scanning and quantitatively analyzing amino acid and organic acid spectra in a biological sample of the newborn by a mass spectrometer, wherein the biological sample of the newborn is a dry blood spot sample; metabolic profile data is obtained that contains quantitative information for a variety of small molecule metabolites. Further, the step of comparing the metabolic spectrogram data with a metabolic phenotype-genotype association knowledge base to automatically identify abnormal metabolic phenotypes meeting preset conditions comprises the following steps: comparing the specific metabolite concentration in the metabolic spectrogram data with a reference concentration range in a pre-constructed metabolic phenotype-genotype correlation knowledge base; Mapping candidate target genetic diseases from a metabolic phenotype-genotype association knowledge base based on a combined pattern of one or more specific metabolites when the concentration of the one or more specific metabolites is identified as continuously deviating from a corresponding reference concentration range; Calculating the associated confidence of each candidate target genetic disease; Only if the association confidence exceeds a preset threshold, determining an abnormal metabolic phenotype associated with the genetic disorder of interest. Further, the construction step of the metabolic phenotype-genotype association knowledge base comprises the following steps: Obtaining metabolic spectrogram data and gene sequencing results from clinically definite genetic disease cases to form a training data set; Extracting characteristics of the metabolic spectrogram data in the training d