Sequence-centric scientific information management

• US 9,633,166 B2
• Filed: 09/21/2015
• Issued: 04/25/2017
• Est. Priority Date: 12/16/2005
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: NextBio
• Inventors: Kupershmidt, Ilya, Su, Qiaojuan Jane
• Primary Examiner(s): SYED, FARHAN M
• Application Number:
  US14/860,412
• Publication Number:
  US 20160132641A1
• Time in Patent Office: 582 Days
• Field of Search: None
• CPC Class Codes: G06F 16/24578 using ranking
• CPC Class Codes: G06F 16/248 Presentation of query results
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/10 Ploidy or copy number detection
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 20/40 Population genetics; Linkage disequilibrium
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 Sequence alignment; Homology search
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/30 Data warehousing; Computing architectures

Abstract

According to various embodiments, aspects of the invention provide a highly efficient meta-analysis infrastructure for performing research queries across a large number of studies and experiments from diverse sequencing technologies as well as different biological and chemical assays, data types and organisms, as well as systems to build and add to such an infrastructure. The methods, systems and apparatuses described enable combining orthogonal types of data and available public knowledge to elucidate mechanisms governing normal development, disease progression, as well as susceptibility of individuals to disease or response to drug treatments.

Claims

1. A computer program product comprising a machine readable non-transitory medium on which is provided program instructions for integrating an instant sequence-centric feature set into a database on a storage device comprising sequence-centric feature sets, the program instructions comprising:

receiving the instant sequence-centric feature set comprising a plurality of sequence regions and associated statistics, wherein each sequence region comprises a genomic sequence or a genomic region;

mapping the plurality of sequence regions of the instant sequence-centric feature set to other sequence regions within the database to provide a set of mapped sequence regions for the instant sequence-centric feature set, wherein the plurality of sequence regions and the other sequence regions within the database are related by genomic coordinate, physical proximity, haplotype, function, or phenotype;

determine ranks of the set of mapped sequence regions in the received sequence-centric feature set and other sequence-centric feature sets in the database, wherein each feature set of the other sequence-centric feature sets comprises a plurality of sequence regions and associated statistics, and wherein the ranks are based on statistics associated with the set of mapped sequence regions;

calculating sequence-sequence scores indicating correlations between the instant sequence-centric feature set and the sequence-centric feature sets in the database using the ranks of the set of mapped sequence regions; and

storing the instant sequence-centric feature set and the sequence-sequence scores in the database on the storage device.

2. The computer program product of claim 1, wherein the database further comprises gene-centric feature sets each comprising a plurality of genes and associated statistics, and wherein the program instructions further comprise:

mapping the plurality of sequence regions of the instant sequence-centric feature set to genes within the database to provide a set of mapped genes for the instant sequence-centric feature set;

determining ranks of the set of mapped genes in the gene-centric feature sets in the database, wherein the ranks are based on statistics associated with the set of mapped genes;

calculating sequence-gene scores indicating correlations between the instant sequence-centric feature set and gene-centric feature sets using the ranks of the set of mapped genes; and

storing the sequence-gene scores in the database on the storage device.

3. A system for integrating an instant sequence-centric feature set into a database comprising sequence-centric feature sets, comprising:

a memory for storing a database of scientific information; and

one or more processors in communication with the memory and configured to;

receive the instant sequence-centric feature set comprising a plurality of sequence regions and associated statistics, wherein each sequence region comprises a genomic sequence or a genomic region;

map the plurality of sequence regions of the instant sequence-centric feature set to other sequence regions within the database to provide a set of mapped sequence regions for the instant sequence-centric feature set, wherein the plurality of sequence regions and the other sequence regions within the database are related by genomic coordinate, physical proximity, haplotype, function, or phenotype;

determine ranks of the set of mapped sequence regions in the received sequence-centric feature set and other sequence-centric feature sets in the database, wherein each feature set of the other sequence-centric feature sets comprises a plurality of sequence regions and associated statistics, and wherein the ranks are based on statistics associated with the set of mapped sequence regions;

calculate sequence-sequence scores indicating correlations between the instant sequence-centric feature set and the sequence-centric feature sets in the database using the ranks of the set of mapped sequence regions; and

store the instant sequence-centric feature set and the sequence-sequence scores in the database on the memory.

4. The system of claim 3, wherein the database further comprises gene-centric feature sets each comprising a plurality of genes and associated statistics, and wherein the one or more processors are further configured to:

map the plurality of sequence regions of the instant sequence-centric feature set to genes within the database to provide a set of mapped genes for the instant sequence-centric feature set;

determine ranks of the set of mapped genes in the gene-centric feature sets in the database, wherein the ranks are based on statistics associated with the set of mapped genes;

calculate sequence-gene scores indicating correlations between the instant sequence-centric feature set and gene-centric feature sets using the ranks of the set of mapped genes, and

store the sequence-gene scores in the database on the memory.

5. The system of claim 3, wherein at least some sequence regions in the instant sequence-centric feature set or the sequence-centric feature sets in the database have different names and are associated with each other, and wherein the instant sequence-centric feature set and the sequence-centric feature sets in the database are obtained from a plurality of experiments, a plurality of platforms, or a plurality of organisms.

6. The system of claim 5, wherein the plurality of sequence regions of the instant sequence-centric feature set and the other sequence regions within the database are mapped to globally unique mapping identifiers.

7. The system of claim 3, wherein the set of mapped sequence regions comprises sequence regions that are found in the sequence-centric feature sets in the database and are associated with the sequence regions in the instant sequence-centric feature set through globally unique mapping identifiers.

8. The system of claim 3, wherein the plurality of sequence regions comprises one or more SNPs, methylated regions, or genomic variations.

9. The system of claim 3, wherein the one or more processors are further configured to:

receive a query sequence region or a query gene as a query input; and

display information based on one or more sequence-sequence scores or one or more sequence-gene scores that correspond to the query sequence region or the query gene.

10. The system of claim 9, wherein the one or more processors are further configured to:

identify feature sets from the sequence-centric feature sets and gene-centric feature sets in the database, wherein the identified feature sets include the query sequence region or the query gene;

obtain a rank of the query sequence region or the query gene in each of the identified feature sets, wherein the rank of the query sequence region or the query gene is based on one or more sequence-sequence scores or one or more sequence-gene scores; and

present a list of the identified feature sets ordered by the rank of the query sequence region or the query gene.

11. The system of claim 4, wherein mapping the plurality of sequence regions of the instant sequence-centric feature set to the other sequence regions or genes within the database comprises mapping sequence regions by genomic coordinate.

12. The system of claim 4, wherein mapping the plurality of sequence regions of the instant sequence-centric feature set to the other sequence regions or genes within the database comprises mapping sequence regions by physical proximity.

13. The system of claim 4, wherein mapping the plurality of sequence regions of the instant sequence-centric feature set to the other sequence regions or genes within the database comprises mapping sequence regions by haplotype.

14. The system of claim 4, wherein mapping the plurality of sequence regions of the instant sequence-centric feature set to the other sequence regions or genes within the database comprises mapping sequence regions by function.

15. The system of claim 4 wherein mapping the plurality of sequence regions of the instant sequence-centric feature set to the other sequence regions or genes within the database comprises mapping sequence regions by phenotype.

16. The system of claim 4, wherein each sequence-sequence score is based on ranks of a first set of features in the instant sequence-centric feature set and ranks of a second set of features in a sequence-centric feature set in the database, wherein the first set of features and the second set of features are mapped to the same globally unique mapping identifiers.