Other

Curagen Corporation

Molecular Staging Inc.

Qlagen Gmbh

Girish Nallur

Stephen F Kingsmore

Barry Schweitzer

Jonathan Marc Rothberg

Xinghua Hu

Disclosed are compositions and methods for detecting small quantities of analytes such as proteins and peptides. The method involves associating a primer with an analyte and subsequently using the primer to mediate rolling circle replication of a circular DNA molecule. Amplification of the DNA circle is dependent on the presence of the primer. Thus, the disclosed method produces an amplified signal, via rolling circle amplification, from any analyte of interest. The amplified DNA remains associated with the analyte, via the primer, and so allows spatial detection of the analyte. The disclosed method can be used to detect and analyze proteins and peptides. Multiple proteins can be analyzed using microarrays to which the various proteins are immobilized. A rolling circle replication primer is then associated with the various proteins using a conjugate of the primer and a molecule that specifically binds the proteins to be detectable. Rolling circle replication from the primers results in production of a large amount of DNA at the sites in the array where the proteins are immobilized. The amplified DNA serves as a readily detectable signal for the proteins. The disclosed method can also be used to compare the proteins expressed in two or more different samples. The information generated is analogous to the type of information gathered in nucleic acid expression profiles. The disclosed method allows sensitive and accurate detection and quantitation of proteins expressed in any cell or tissue.

Protein expression profiling

The present invention describes methods and devices for sequencing a polynucleotide by determining subsets of composite subsequences present in nucleic acid subsamples generated from the sample polynucleotide. A hairpin primer interrogates the composite subsequences in a two-step process resulting first in a polymerase extended product whose synthesis identifies the first subsequence of the composite subsequence. The second subsequences are identified by hybridizing the polymerase extended products or amplified products therefrom to an array of capture probes wherein each capture probe is positionally distinguishable from other capture probes. The invention is applicable to the quantitative determination of the presence of nucleic acids in a sample, for identifying differences in the relative abundance of nucleic acids in a mixture of nucleic acids, and generally, to diagnostic aids for the identification of nucleic acids.

Sequencing a polynucleotide on a generic chip

This invention includes methods for identifying nucleic acids in a sample of nucleic acids by observing sequence sets present in the nucleic acids of the sample and then identifying those sequences in a nucleic acid sequence database having the sequence sets observed. In a preferred embodiment, a sequence set consists of two primary subsequences and an additional subsequence having determined mutual relationships. The methods include those for observing the sequence sets and those for performing sequence database searches. This invention also includes devices for recognizing in parallel the additional subsequences in a sample of as well as methods for the use of these devices. In a preferred embodiment, the devices include probes bound to a planar surface that recognize additional subsequence by hybridization, and the methods of use include features to improve the specificity and reproducibility of this hybridization.

Methods and devices for measuring differential gene expression

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Guilford, CT, United States of America

Girish Nallur