Methods of optimizing genome assembly parameters

A system comprising one or more computer processor circuits configured and arranged to:

• select a k-mer-based de novo genome assembler program, designated assembler;
• provide a set of parameters for assembly of a set of sequenced nucleic acids, the parameters having respective values and respective priority scores, the parameters including a k-mer parameter having an initial length k in number of nucleotides, k being a positive integer equal to at least 35;
• provide a set of quality metrics for assembly of a set of sequenced nucleic acids, the quality metrics having respective weights indicating importance, respective target values, and respective computed values calculated during assembly, a given quality metric depending on one or more of the parameters;
• initiate assembly of the set of sequenced nucleic acids by the assembler, the assembler utilizing the set of parameters and the set of quality metrics, thereby forming intermediate assembled sequences;
• perform a procedure iteratively until the respective computed values of the quality metrics equal the respective target values, the procedure comprising the steps of:
• i) stopping the assembler when the respective computed values of the quality metrics do not equal the respective target values, ii) modifying at least one of the parameters and/or at least one of the quality metrics, iii) deleting any intermediate assembled sequences, iv) initiating assembly of the set of sequenced nucleic acids by the assembler, and v) calculating values of the quality metrics including any modified quality metrics, the procedure terminating while utilizing a set of final parameters and a set of final quality metrics, the final parameters including a final k-mer parameter of length k′;
• and
• complete assembly of the set of sequenced nucleic acids using the assembler, the set of final parameters, and the set of final quality metrics, thereby forming one or more final assembled genomes.

A computer program product, comprising a computer readable hardware storage device having a computer-readable program code stored therein, said program code configured to be executed by a processor of a computer system to implement a method comprising:

• selecting a k-mer-based de novo genome assembler program, designated assembler;
• providing a set of parameters for assembly of a set of sequenced nucleic acids, the parameters having respective values and respective priority scores, the parameters including a k-mer parameter having an initial length k in number of nucleotides, k being a positive integer equal to at least 35;
• providing a set of quality metrics for assembly of a set of sequenced nucleic acids, the quality metrics having respective weights indicating importance, respective target values, and respective computed values calculated during assembly, a given quality metric depending on one or more of the parameters;
• initiating assembly of the set of sequenced nucleic acids by the assembler, the assembler utilizing the set of parameters and the set of quality metrics, thereby forming intermediate assembled sequences;
• performing a procedure iteratively until the respective computed values of the quality metrics equal the respective target values, the procedure comprising the steps of:
• i) stopping the assembler when the respective computed values of the quality metrics do not equal the respective target values, ii) modifying at least one of the parameters and/or at least one of the quality metrics, iii) deleting any intermediate assembled sequences, iv) initiating assembly of the set of sequenced nucleic acids by the assembler, and v) calculating values of the quality metrics including any modified quality metrics, the procedure terminating while utilizing a set of final parameters and a set of final quality metrics, the final parameters including a final k-mer parameter of length k′;
• and
• completing assembly of the set of sequenced nucleic acids using the assembler, the set of final parameters, and the set of final quality metrics, thereby forming one or more final assembled genomes.

A method of genome assembly for single assembly or sets of assemblies by optimizing the k-mer length parameter, the method comprising the following steps:

• using high throughput sequencing to sequence one or more genomes, thereby forming sequence data;
• processing the sequence data for quality control;
• selecting a quality metric for assembly of the sequence data, the quality metric having a calculated value during an assembly and a target value;
• initiating assembly of the sequence data using a set of k-mer values for the one or more genomes, the k-mer values having scores and ranks;
• performing a procedure during the assembly when the calculated value of the quality metric does not equal to the target value, the procedure comprising:
• a) deleting any intermediate assembled sequences,
• b) modifying the k-mer values,
• c) initiating assembly using the modified k-mer values,
• d) assessing the calculated value of the quality metric relative to the target value before the assembly is complete;
• e) updating the scores and ranks of the k-mer values;
• repeating the procedure until the calculated value of the quality metric equals the target value;
• and
• completing the assembly.