Method for selecting anticancer agent based on protein damage information of individual to prevent anticancer agent side effects
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Publication Number
US-11195594-B2
Publication Date
2021-12-07
Expiration Date
Abstract
The present invention relates to a method and a system for selecting an anticancer agent based on protein damage information of an individual by using individual genome sequencing. The method and the system, according to the present invention, are highly reliable and widely applicable techniques capable of predicting side effects or risks of specific drugs, in other words, anticancer agents, for each individual by performing sequence analysis of an exon part of a gene that codes various proteins involved in pharmacokinetics or pharmacodynamics of anticancer agents.
Core Innovation
The invention relates to providing information for selecting an anticancer agent using individual genome sequence variation. It determines gene sequence variation information of one or more genes involved in pharmacodynamics or pharmacokinetics of an anticancer agent from individual genome sequence information. The gene sequence variation score is calculated as a numerical score indicating a degree of variation that causes amino acid sequence variation in a protein encoded by the gene or causes a transcription control variation, thereby causing change or damage to a structure or function of the protein.
The invention calculates an individual protein damage score by aggregating gene sequence variation scores using a weighted equation. The protein damage score corresponds to a protein encoded by a gene g, and the aggregation uses weighting assigned to each gene sequence variation score among target sequence variations of the gene. Based on the individual protein damage scores, the invention calculates an individual drug score for a drug d by aggregating the protein damage scores of proteins encoded by one or more genes involved in pharmacodynamics or pharmacokinetics of the drug, again using weighting assigned to each protein damage score.
The invention provides the calculated individual drug score for use in drug selection among anticancer agents. In a system implementation, a database can be searched or extracted for information relevant to a gene or protein related to an anticancer agent applicable to an individual, and computer instructions calculate the gene sequence variation information, gene sequence variation score, individual protein damage score, and individual drug score. A display unit displays information regarding the calculated scores for use in drug selection among anticancer agents.
Claims Coverage
The document includes two independent claims that together cover (i) a method for providing an individual drug score for selecting an anticancer agent from individual genome sequence variation and (ii) a system configured to calculate and display the same scores from stored/computer-accessible gene/protein information. The main inventive features are organized below by each independent claim.
Scoring framework for selecting anticancer agents from individual genome sequence variation
Determining gene sequence variation information of one or more genes involved in pharmacodynamics or pharmacokinetics of an anticancer agent from individual genome sequence information; calculating a gene sequence variation score that indicates a degree of variation causing an amino acid sequence variation or a transcription control variation and thereby causes change or damage to a structure or function of the encoded protein; calculating an individual protein damage score using an equation that aggregates gene sequence variation scores with weighting assigned to each sequence variation; calculating an individual drug score using an equation that aggregates protein damage scores of proteins encoded by one or more genes involved in pharmacodynamics or pharmacokinetics of the drug with weighting assigned to each protein damage score; and providing the individual drug score for use in drug selection among anticancer agents.
Database- and instruction-based system for computing individual drug score
Providing a database and communication unit for searching or extracting information relevant to a gene or protein related to an anticancer agent; storing computer instructions on a non-transitory computer-readable medium including instructions to calculate gene sequence variation information, calculate a gene sequence variation score, calculate an individual protein damage score using the equation for protein damage with weighting, and calculate an individual drug score using the equation for drug score with weighting; and providing a display unit configured to display information regarding the calculated scores for use in drug selection among anticancer agents.
Collectively, the independent claims define an explicit scoring pipeline from individual genome sequence variation to a gene sequence variation score, an individual protein damage score, and an individual drug score, where both scores use weighted aggregation equations, and where a system implementation uses a database, executable computer instructions, and a display unit to compute and present the drug selection information.
Stated Advantages
Provides an individual drug score for use in drug selection among anticancer agents.
Documented Applications
Personalized anticancer-agent selection using individual genome sequence variation to support side-effect risk prediction for anticancer agents (e.g., busulfan in pediatric leukemia; mercaptopurine/thiopurine-based drugs).
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