Pacific Biosciences of California, Inc.

Omnibiocomputing LLC

Pacific Biosciences for California, Inc.

Chen-Shan Chin

Patrick Marks

Stephen Wilson Turner

Paul S Peluso

Jon M Sorenson

David R Rank

Asif Khalak

David Alexander

Aaron Klammer

Wangchang Hou

Susan Tang

Exemplary embodiments provide methods and systems for string graph assembly of polyploid genomes. Aspects of the exemplary embodiment include receiving a string graph generated from sequence reads of at least 0.5 kb in length; identifying unitigs in the string graph and generating a unitig graph; and identifying string bundles in the unitig graph by: determining a primary contig from each of the string bundles; and determining associated contigs that contain structural variations compared to the primary contig.

String graph assembly for polyploid genomes

Methods, systems, and devices are contemplated for assembling a genome from duplicate segments of the genome. Sequences with a first level of common neighboring base pairs are identified and organized into first level groups. Groups are then identified from the first level groups that have a second level of common neighboring base pairs and organized into a number of second level groups. A third level of groups can further be organized in some embodiments. Typically the second level groups are assembled into spans having contiguous base pair sequences, which are then assembled into the broader genome sequence. The inventive subject matter is preferably used for whole genome sequencing.

High efficient indexing method for genome assembly

Exemplary embodiments provide methods and systems for diploid genome assembly and haplotype sequence reconstruction. Aspects of the exemplary embodiment include generating a fused assembly graph from reads of both haplotypes, the fused assembly graph including identified primary contigs and associated contigs; generating haplotype-specific assembly graphs using phased reads and haplotype aware overlapping of the phased reads; merging the fused assembly graph and haplotype-specific assembly graphs to generate a merged assembly haplotype graph; removing cross-phasing edges from the merged assembly haplotype graph to generate a final haplotype-resolved assembly graph; and reconstructing haplotype-specific contigs from the final haplotype-resolved assembly graph resulting in haplotype-specific contigs.

De novo diploid genome assembly and haplotype sequence reconstruction

The present invention is generally directed to a hierarchical genome assembly process for producing high-quality de novo genome assemblies. The method utilizes a single, long-insert, shotgun DNA library in conjunction with Single Molecule, Real-Time (SMRT&#xae;) DNA sequencing, and obviates the need for additional sample preparation and sequencing data sets required for previously described hybrid assembly strategies. Efficient de novo assembly from genomic DNA to a finished genome sequence is demonstrated for several microorganisms using as little as three SMRT&#xae; cells, and for bacterial artificial chromosomes (BACs) using sequencing data from just one SMRT&#xae; Cell. Part of this new assembly workflow is a new consensus algorithm which takes advantage of SMRT&#xae; sequencing primary quality values, to produce a highly accurate de novo genome sequence, exceeding 99.999% (QV 50) accuracy. The methods are typically performed on a computer and comprise an algorithm that constructs sequence alignment graphs from pairwise alignment of sequence reads to a common reference.

Hierarchical genome assembly method using single long insert library

The present invention is generally directed to powerful and flexible methods and systems for consensus sequence determination from replicate biomolecule sequence data. It is an object of the present invention to improve the accuracy of consensus biomolecule sequence determination from replicate sequence data by providing methods for assimilating replicate sequence into a final consensus sequence more accurately than any one-pass sequence analysis system.

Growing community of inventors

San Leandro, CA, United States of America

Chen-Shan Chin