Genome Explorer System to Process and Present Nucleotide Variations in Genome Sequence Data

• US 20140115515A1
• Filed: 10/24/2013
• Published: 04/24/2014
• Est. Priority Date: 10/24/2012
• Status: Active Grant

• Current Assignee: NantOmics, LLC (NantWorks, LLC)
• Original Assignee: Complete Genomics Incorporated (BGI Genomics Co., Ltd.)
• Inventors: Adams, Julie, Buholzer, Mirko
• Granted Patent: US 10,347,361 B2
• Time in Patent Office: Days
• US Class Current: 715/771
• 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 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 45/00 ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/10 Ontologies; Annotations

Abstract

This disclosure provides a technology for users to gain first-hand knowledge and experience with interpreting whole genomes. The technology graphically depicts variations in genome sequences in an expandable display, and provides a platform whereby the user may find and research the biological significance of such variants. The technology also provides a unique collaborative environment designed to capture and improve the collective knowledge of the participating community.

Claims

1. A method for displaying variations between complex sequences, the method comprising:

(a) receiving a sample complex sequence for a test sample;

(b) aligning, with a computer system, the sample complex sequence with a reference complex sequence for a reference sample;

(c) identifying, with the computer system, a plurality of variations between the sample complex sequence and the reference complex sequence;

(d) providing a user interface for controlling a display of a comparative gene sequence map, the display showing where the plurality of variations are located;

(e) receiving, at the user interface, a selection of a region within the genetic sequence map, the region being less than half the entire comparative gene sequence map; and

(f) reconfiguring the display of the comparative gene sequence map such that the region is magnified.

2. The method of claim 1, wherein the region is magnified in proportion to the size of the region.

3. The method of claim 1, wherein the region is magnified at least two times.

4. The method of claim 1, wherein the region is magnified such that the region is presented across at least about half of the width of the display.

5. The method of any preceding claim, further comprising:

determining whether the region is smaller than a specified size;

if the region is smaller than the specified size;

displaying a nucleotide sequence that spans the region, and

displaying the locations of one or more variations in the nucleotide sequence.

6. The method of claim 1, wherein the plurality of variations includes copy number variations (CNVs), small nucleotide variations (SNVs), and loss of heterozygosity (LOH).

7. The method of claim 1, wherein the display presents separate graphs across the region of interest for copy number, allele specific copy number, and protein encoding sequences.

8. The method of claim 1, wherein a user may select a karyogram view, a circular view across one or more chromosomes, or a linear view of a region of interest, any of which indicate where variations in complex sequence occur.

9. The method of claim 1, wherein step (a) comprises:

(i) receiving a first identifier identifying a user and a second identifier identifying a test sample;

(ii) determining whether the user has authority to access sequence data for the test sample; and

if so,

(iii) retrieving complex sequence for the test sample from a secure database, the secure database including genomes for a plurality of different samples.

10. The method of claim 1, wherein step (a) comprises sequencing DNA contained in the test sample, thereby obtaining complex sequence for the test sample.

11. The method of claim 1, wherein step (b) comprises iteratively:

(i) sourcing complex sequence for any one of a plurality of a reference samples in a reference database;

(ii) comparing the complex sequence for the test sample with the complex sequence sourced in step (i);

(iii) selecting the reference sourced in step (i) as a suitable reference for analyzing the complex sequence for the test sample if it matches the test sample according to preset criteria.

12. The method of claim 1, further comprising receiving a selection of a filter that specifies characteristics of sequence variations to be displayed;

and adapting the display to highlight variations having the characteristics and/or remove variations not having the characteristics specified by the filter.

13. The method of claim 1, further comprising predicting one or more effect(s) of each of at least some of the variations identified in step (c) on protein expression, protein function, clinical presentation, and/or disease risk, and providing information about the effect(s) with the gene sequence map in step (d).

14. The method of claim 1, further comprising comparing at least some of the variations identified in step (c) with known variants, and providing information about the known variants with the gene sequence map in step (d).

15. The method of claim 14, wherein the information about the known variants has been obtained at least in part from external databases.

16. The method of claim 1, further comprising receiving a selection of one or more of the variations in DNA sequence identified in step (c), and indicating the one or more variations on the comparative genetic map displayed in step (d).

17. The method of claim 1, further comprising:

receiving a selection of one or more of the variations in DNA sequence identified in step (c), determining the position of each of the selected variations in the human genome, obtaining information about DNA sequence variations observed for other samples at or around the position for at least some of the selected variations, and providing a display comprising the information.

18. The method of claim 1, further comprising:

receiving, at the user interface, an annotation for one or more of the variations in DNA sequence identified in step (c); and

displaying the annotation on the comparative genetic map displayed in step (d).

19. The method of claim 1, further comprising:

receiving from a second user interface an annotation for one or more of the variations in DNA sequence identified in step (c); and

indicating the annotation on the comparative genetic map displayed in step (d).

20. The method of claim 18, further comprising:

providing on the comparative genetic map displayed in step (d) at or near each of one or more of the variations in DNA sequence identified in step (c) a hyperlink to a forum whereby a plurality of users having access to the complex sequence may exchange first information and reply information regarding the respective variation.

21. A computer product comprising a non-transitory computer readable medium storing a plurality of instructions that when executed control a computer system to perform the method of claim 1.

22. A system configured to calculate and provide a display of variations in complex sequence data of a test sample relative to complex sequence data for a reference sample according to the method of claim 1.

23. The system of claim 22, comprising a computer processor, a database storing the reference DNA sequence data, and a DNA sequencer.

24. The system of claim 21, wherein the system is configured so that the user may share information with others about one or more variations identified in step (d).

25. A server system for sharing variations in complex sequences between clients, the server system comprising one or more processors configured to:

assemble a gene sequence map that shows a plurality of variations between a sample complex sequence for a test sample and a reference complex sequence for a reference sample;

provide the gene sequence map to a plurality of clients;

provide a first user interface to a first client, wherein the user interface is configured to;

receive directions to make the gene sequence map available to other clients; and

receive first information about one or more of the variations made available to the other clients;

provide a second user interface to one or more second clients;

receive reply information from the one or more second clients about the one or more variations made available; and

provide, to the first client, the reply information for the one or more variations.

26. The server system of claim 25, wherein the gene sequence map is provided to the plurality of clients with links from one or more of the variations to first information and reply information for the respective variation.

27. The server system of claim 25, wherein the first information about the one or more variations provided by the first client user is made available to other clients with hyperlinks that link to an indication of the one or more variations on the gene sequence map.

28. The server system of claim 27, wherein the first information is displayed in a feed as one or more entries, the feed being available to a plurality of users, wherein each entry corresponds to a respective variation.

29. The server system of claim 27, wherein the first information about the one or more variations is made available to the other users by way of an information website on the Internet.

30. The server system of claim 28, wherein the server is configured to compile reply information about one or more of the variations from other users into an assessment as to whether the variation(s) are pathogenic or benign.