Complete Genomics

Complete Genomics created this resource center to provide a place to get information about the latest advances in human DNA sequencing and related areas.

To learn more about Complete Genomics’ products you can download the following white papers.

Complete Genomics Technology Papers:

Other Scientific Papers:

1.- Accurate Multiplex Polony Sequencing of an Evolved Bacterial Genome Jay Shendure, Gregory J. Porreca, Nikos B. Reppas, Xiaoxia Lin, John P. McCutcheon, Abraham M. Rosenbaum, Michael D. Wang, Kun Zhang, Robi D. Mitra, and George M. Church
Science 9 September 2005, 309: 1728-1732; published online 4 August 2005 [DOI: 10.1126/science.1117389] (in Reports)

Author’s Abstract: We describe a DNA sequencing technology in which a commonly available, inexpensive epifluorescence microscope is converted to rapid nonelectrophoretic DNA sequencing automation. We apply this technology to resequence an evolved strain of Escherichia coli at less than one error per million consensus bases. A cell-free, mate-paired library provided single DNA molecules that were amplified in parallel to 1-micrometer beads by emulsion polymerase chain reaction. Millions of beads were immobilized in a polyacrylamide gel and subjected to automated cycles of sequencing by ligation and four-color imaging. Cost per base was roughly one-ninth as much as that of conventional sequencing. Our protocols were implemented with off-the-shelf instrumentation and reagents.

2.- Identification of APC Gene Mutations in Colorectal Cancer Using Universal Microarray-based Combinatorial Sequencing-by-Hybridization
Shannon Cowie, Snezana Drmanac, Donald Swanson, Kathleen Delgrosso, Steve Huang, Desiree du Sart, Radoje Drmanac, Saul Surrey and Paolo Fortina
Human Mutation 24: 261-271, 2004

Author’s Abstract: Familial adenomatous polyposis (FAP) is an autosomal dominant inherited form of colorectal cancer, caused mostly by mutations in the APC gene. Read more…

3.- Sequencing by Hybridization (SBH): Advantages, Achievements, and Opportunities
Radoje Drmanac, Snezana Drmanac, Gloria Chui, Robert Diaz, Aaron Hou, Hui Jin, Paul Jin, Sunhee Kwon, Scott Lacy, Bill Moeur, Jay Shafto, Don Swanson, Tatjana Ukrainczyk, Chongjun Xu, Deane Little
Advances in Biochemical Engineering/Biotechnology, Vol. 77 75-101, 2002

Author’s Abstract: Efficient DNA sequencing of the genomes of individual species and organisms is a critical task for the advancement of biological sciences, medicine and agriculture. Read more…

4.- Accurate sequencing by hybridization for DNA diagnostics and individual genomics
Snezana Drmanac, David Kita, Ivan Labat, Brian Hauser, Carl Schmidt, John D. Burczak & Radoje Drmanac Nature Biotechnology 16, 54 - 58 (1998) doi:10.1038/nbt0198-54 (in Articles)

Author’s Abstract: Medical DNA diagnostics will increasingly rely on an accurate and inexpensive identification of mutations that affect the function of a gene. To validate diagnostic sequencing by hybridization (SBH), a number of p53 samples were analyzed with the complete set of 8192 noncomplementary 7-mer oligonu-cleotides. In four repeated, blind experiments we accurately sequenced 1.1 kb per each of 12 homozygote and heterozygote samples possessing base substitutions, insertions, and deletions. This SBH variant offers a high throughput platform to inexpensively sequence individual gene or pathogen genome samples within the clinical laboratory setting.

5.- Gene-representing cDNA clusters defined by hybridization of 57,419 clones from infant brain libraries with short oligonucleotide probes
S. Drmanac, N. A. Stavropoulos, I. Labat, J. Vonau, B. Hauser, M. B. Soares and R. Drmanac
Genomics Volume 37, Issue 1, 1996, Pages 29-40

Author’s Abstract: Diverse biochemical and computational procedures and facilities have been developed to hybridize thousands of DNA clones with short oligonucleotide probes and subsequently to extract valuable genetic information. This technology has been applied to 73,536 cDNA clones from infant brain libraries. By a mutual comparison of 57,419 samples that were successfully scored by 200-320 probes, 19,726 genes have been identified and sorted by their expression levels. The data indicate that an additional 20,000 or more genes may be expressed in the infant brain. Representative clones of the found genes create a valuable resource for complete sequencing and functional studies of many novel genes. These results demonstrate the unique capacity of hybridization technology to identify weakly transcribed genes and to study gene networks involved in organismal development, aging, or tumorigenesis by monitoring the expression of every gene in related tissues, whether known or still undiscovered.

The papers below describe the fundamentals of sequencing by hybridization (SBH).

6.- DNA sequence determination by hybridization: a strategy for efficient large-scale sequencing R Drmanac, S Drmanac, Z Strezoska, T Paunesku, I Labat, M Zeremski, J Snoddy, WK Funkhouser, B Koop, L Hood, et al. Science 11 June 1993 260: 1649-1652 [DOI: 10.1126/science.8503011] (in Articles)

Author’s Abstract: The concept of sequencing by hybridization (SBH) makes use of an array of all possible n-nucleotide oligomers (n-mers) to identify n-mers present in an unknown DNA sequence. Computational approaches can then be used to assemble the complete sequence. As a validation of this concept, the sequences of three DNA fragments, 343 base pairs in length, were determined with octamer oligonucleotides. Possible applications of SBH include physical mapping (ordering) of overlapping DNA clones, sequence checking, DNA fingerprinting comparisons of normal and disease-causing genes, and the identification of DNA fragments with particular sequence motifs in complementary DNA and genomic libraries. The SBH techniques may accelerate the mapping and sequencing phases of the human genome project.

7.- Prospects for a Miniaturized, Simplified and Frugal Human Genome Project
Radoje Drmanac and Radomir Crkvenjakov
Genetic Engineering Center, P.O. Box 794, 11000, Belgrade, Yugoslavia
Scientia Yugoslavica 1990 16(1-2)97-107

Author’s Abstract: The knowledge about parts or entire genomes on the level of primary structure as well as the possibility of following inheritance using this information are being increasingly recognized as conditions for more efficient and faster study of biological processes. Read more…

8.- Sequencing of megabase plus DNA by hybridization: Theory of the method
Radoje Dramanac, Ivan Labat, Ivan Brukner and Radomir Crkvenjakov
Genetic Engineering Center, P.O. Box 794, 11000, Belgrade, Yugoslavia
Genomics Volume 4, Issue 2, 1989, Pages 114-128

Author’s Abstract: A mismatch-free hybridization of oligonucleotides containing from 11 to 20 monomers to unknown DNA represents, in essence, a sequencing of a complementary target. Realizing this, we have used probability calculations and, in part, computer simulations to estimate the types and numbers of oligonucleotides that would have to be synthesized in order to sequence a megabase plus segment of DNA. We estimate that 95,000 specific mixes of 11-mers, mainly of the 5′ (A,T,C,G)(A,T,C,G)N8(A,T,C,G)3′ type, hybridized consecutively to dot blots of cloned genomic DNA fragments would provide primary data for the sequence assembly. An optimal mixture of representative libraries in M13 vector, having inserts of (i) 7kb, (ii) 0.5 kb genomic fragments randomly ligated in up to 10-kb inserts, and (iii) tandem “jumping” fragments 100 kb apart in the genome, will be needed. To sequence each million base pairs of DNA, one would need hybridization data from about 2100 separate hybridization sample dots. Inevitable gaps and uncertainties in alignment of sequenced fragments arising from nonrandom or repetitive sequence organization of complex genomes and difficulties in cloning “poisonous” sequences in Escherichia coli, inherent to large sequencing by any method, have been considered and minimized by choice of libraries and number of subclones used for hybridization. Because it is based on simpler biochemical procedures, our method is inherently easier to automate than existing sequencing methods. The sequence can be derived from simple primary data only by extensive computing. Phased experimental tests and computer simulations increasing in complexity are needed before accurate estimates can be made in terms of cost and speed of sequencing by the new approach. Nevertheless, sequencing by hybridization should show advantages over existing methods because of the inherent redundancy and parallelism in its data gathering.