Wisconsin Alumni Research Foundation

New York University

Columbia University

Other

National Institutes of Health, a Component of the US Dept. of Health & Human Services

University of Chicago

Industry-university Cooperation Foundation Sogang University

National Institutes of Health

University of Leiden

U.S. Government Nih Division of Extramural Inventions and Technology Resources

David Charles Schwartz

Bhubaneswar Mishra

Juan Jose De Pablo

Kyubong Jo

Charles Cantor

Thomas S Anantharaman

Konstantinos Dimitrios Potamousis

Michael A Newton

Kristy Leigh Kounovsky-Shafer

Christopher P Churas

Theo Odijk

Juan Pablo Hernandez-Ortiz

Dalia M Dhingra

Daniel K Forrest

Eileen T Dimalanta

Rodney Runnheim

Salvatore Paxia

Marco Antoniotti

Seong Hyun Lee

Tian Wu

Kyu Bong Jo

Galex S Yen

Shiguo Zhou

Steven J Goldstein

Jessica Severin

Subhrangshu Nandi

Konstantinos D Potamousis

Rodney A Runnheim

Systems and methods for identifying sequence information from measurements made on single nucleic acid molecules are disclosed. The systems and methods can include binding portions of nucleic acid molecules with marker molecules, such as fluorescent molecules and/or intercalating molecules. The marker molecules provide a detectable signal that includes information about the underlying genomic information of the location on the nucleic acid molecule where a given marker molecule is bound. A profile of the detectable signal along a position of the nucleic acid is acquired for multiple different nucleic acid molecules. The PRIMR algorithm processes the data to provide a consensus profile from which a consensus underlying genomic information can be determined.

Systems and methods for identifying sequence information from single nucleic acid molecule measurements

Devices, systems, and methods for en masse patterning of nucleic acid molecule structures are disclosed. The devices can include microchannels and nanoslits. The microchannels and nanoslits can be connected by parking chambers. The systems and methods can utilize the geometry of the devices in coordination with a voltage application routine to park nucleic acid molecules in the parking chambers and subsequently inject the nucleic acid molecules into the nanoslits. The methods can be utilized to present nucleic acid molecules in a fashion suitable for genomic analysis. The methods can also be utilized to provide size selection of the nucleic acid molecules.

System and method for en masse patterning of molecule structures

The present invention relates to a composition for DNA staining, which can be safely used for researchers, can prevent DNA photocleavage, and can be applied to various fields. According to the present invention, when DNA is stained by using a fluorescent protein and a particular peptide bound to DNA, such a fluorescent protein-peptide is safe to researchers, suppresses DNA photocleavage, and allows reversible staining, thereby enabling efficient DNA staining. Therefore, the composition for DNA staining of the present invention can be variously used in DNA-related research.

Composition comprising DNA binding peptide for DNA staining

Methods are provided for tagging, characterizing and sorting double-stranded biomolecules while maintaining the integrity of the biomolecules.

Method of DNA analysis using micro/nanochannel

There are provided computer systems for visualizing and annotating single molecule images. Annotation systems in accordance with this disclosure allow a user to mark and annotate single molecules of interest and their restriction enzyme cut sites thereby determining the restriction fragments of single nucleic acid molecules. The markings and annotations may be automatically generated by the system in certain embodiments and they may be overlaid translucently onto the single molecule images. An image caching system may be implemented in the computer annotation systems to reduce image processing time. The annotation systems include one or more connectors connecting to one or more databases capable of storing single molecule data as well as other biomedical data. Such diverse array of data can be retrieved and used to validate the markings and annotations. The annotation systems may be implemented and deployed over a computer network. They may be ergonomically optimized to facilitate user interactions.

Computer systems for annotation of single molecule fragments

There is provided a high throughput automated single molecule image collection and processing system that requires minimal initial user input. The unique features embodied in the present disclosure allow automated collection and initial processing of optical images of single molecules and their assemblies. Correct focus may be automatically maintained while images are collected. Uneven illumination in fluorescence microscopy is accounted for, and an overall robust imaging operation is provided yielding individual images prepared for further processing in external systems. Embodiments described herein are useful in studies of any macromolecules such as DNA, RNA, peptides and proteins. The automated image collection and processing system and method of same may be implemented and deployed over a computer network, and may be ergonomically optimized to facilitate user interaction.

Automated imaging system for single molecules

A computer database system for storing, processing, displaying, and analyzing single molecule data is capable of managing and processing variously formatted, different kinds of single molecule data and displaying subsets thereof upon instructions by a user. A component-based architecture is implemented where the processing and the displaying are separately performed. The data is dynamically loaded for processing as needed. Embodiments of computer database systems can be utilized in managing single molecule data, particularly image data derived from single molecule images. Such single molecule images may be generated by a variety of technologies, e.g., optical mapping, atomic force microscopy (AFM), scanning tunneling microscopy (STM), and flow cytometry. Systems may be deployed over a computer network. One or more additional databases may be included which are interconnected through a network.

Computer database system for single molecule data management and analysis

Methods are provided for ascertaining the sequence of a genomic DNA sample by nicking the DNA sample with a restriction nicking enzyme, followed by nick translation with labeled nucleotides, such that the labeled nucleotides can be quantified and compared to a known, reference genome.

Methods of whole genome analysis

Laminar flow of a carrier liquid and polymeric molecules through micro-channels is used to straighten the polymeric molecules and attach the straightened molecules to a wall of the micro-channel for subsequent treatment and analysis. Micro-channels can be manufactured using an elastic molding material. One micro-channel embodiment provides fluid flow using a standard laboratory centrifuge.

Micro fluidic system for single molecule imaging

Arrays of distinct chemically reactive materials used for assaying or screening are assembled by arranging premanufactured strips, each having a linear array of chemically reactive materials on its surface, into a frame to be exposed to a substance to be analyzed. The strips provide great flexibility in generating different types of arrays while still permitting efficiencies to be gained by batch processing of each strip type. The arrays further provide for novel read-out and reaction promotion techniques making use of the ability of the strips to direct and received energy to and from particular sites.

Chemical screening system using strip arrays

A method and system are provided for comparing ordered segments of a first DNA restriction map with ordered segments of a second DNA restriction map to determine a level of accuracy the first DNA map and/or the second DNA map. In particular, the first and second DNA maps can be received (the first DNA map corresponding to a sequence DNA map, and the second DNA map corresponding to a genomic consensus DNA map as provided in an optical DNA map). Then, the accuracy of the first DNA map and/or the second DNA map is validated based on information associated with the first and second DNA maps. In addition, a method and system are provided for aligning a plurality of DNA sequences with a ordered DNA restriction map. The DNA sequences and the DNA map are received (the DNA sequences being fragments of a genome and the DNA map corresponding to a genomic consensus DNA map which relates to an optical ordered DNA map). Then, a level of accuracy of the DNA sequences and the DNA map is obtained based on information associated with the DNA sequences and the DNA map by means of the method and system described above. The locations of the DNA map at which the DNA sequences are capable of being associated with particular segments of the DNA map are located. Furthermore, it is possible to obtain locations of the DNA map (without the validation) by locating an optimal one of the locations for each of the DNA sequences for each of the locations.

System and process for validating, aligning and reordering one or more genetic sequence maps using at least one ordered restriction map

Laminar flow of a carrier liquid and polymeric molecules through micro-channels is used to straighten, align, separate, and/or sort the polymeric molecules. The polymeric molecules may be analyzed and/or manipulated in the carrier liquid or attached to a wall of the micro-channel for subsequent treatment and analysis. Micro-channels can be manufactured using an elastic molding material. One micro-channel embodiment provides fluid flow using a standard laboratory centrifuge.

Micro-channel long molecule manipulation system

A method for observing and determining the size of individual molecules and for determining the weight distribution of a sample containing molecules of varying size, which involves placing a deformable or nondeformable molecule in a medium, subjecting the molecule to an external force, thereby causing conformational and/or positional changes, and then measuring these changes. Preferred ways to measure conformational and positional changes include: (1) determining the rate at which a deformable molecule returns to a relaxed state after termination of the external force, (2) determining the rate at which a molecule becomes oriented in a new direction when the direction of the perturbing force is changed, (3) determining the rate at which a molecule rotates, (4) measuring the length of a molecule, particularly when it is at least partially stretched, or (5) measuring at least one diameter of a spherical or ellipsoidal molecule. Measurements of relaxation, reorientation, and rotation rates, as well as length and diameter can be made using a light microscope connected to an image processor. Molecule relaxation, reorientation and rotation also can be determined using a microscope combined with a spectroscopic device. The invention is particularly useful for measuring polymer molecules, such as nucleic acids, and can be used to determine the size and map location of restriction digests. Breakage of large polymer molecules mounted on a microscope slide is prevented by condensing the molecules before mounting and unfolding the molecules after they have been placed in a matrix.

Growing community of inventors

Madison, WI, United States of America

David Charles Schwartz