序号 专利名 申请号 申请日 公开(公告)号 公开(公告)日 发明人
181 Methods and systems for genetic analysis US15222875 2016-07-28 US09745626B2 2017-08-29 Gabor T. Bartha; Gemma Chandratillake; Richard Chen; Sarah Garcia; Hugo Yu Kor Lam; Shujun Luo; Mark R. Pratt; John West
This disclosure provides systems and methods for sample processing and data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Some or all of a nucleic acid sample may be sequenced to provide sequence information, which may be stored or otherwise maintained in an electronic storage location. The sequence information may be analyzed with the aid of a computer processor, and the analyzed sequence information may be stored in an electronic storage location that may include a pool or collection of sequence information and analyzed sequence information generated from the nucleic acid sample. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample, for producing one or more libraries, and for producing biomedical reports. Methods and systems of the disclosure can aid in the diagnosis, monitoring, treatment, and prevention of one or more diseases and conditions.
182 Methods, systems, and software for identifying bio-molecules using models of multiplicative form US14167713 2014-01-29 US09684771B2 2017-06-20 Gregory Allan Cope; Nicholas John Agard
The present invention provides methods for identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. More specifically, some embodiments of the present invention provide methods for building sequence-activity models comprising multiplicative terms and using the models to guide directed evolution. In some embodiments, the sequence-activity models include one or more interaction terms, each of which including an interaction coefficient representing the contribution to activity of two or more defined residues. In some embodiments, the models describe relation between protein or nucleic acid sequences and protein activities. In some embodiments, the present invention also provides methods for preparing sequence-activity models, including but not limited to stepwise addition or subtraction techniques, Bayesian regression, ensemble regression and other methods. The present invention further provides digital systems and software for performing the methods provided herein.
183 Universal Fibronectin Type III Bottom-Side Binding Domain Libraries US14828763 2015-08-18 US20160194626A1 2016-07-07 Andreas LOEW; Brian VASH
The invention pertains to a natural-variant combinatorial library of fibronectin Type 3 domain (Fn3) polypeptides useful in screening for the presence of one or more polypeptides having a selected binding or enzymatic activity. The library polypeptides include (a) regions A, AB, B, C, CD, D, E, EF, F, and G having wildtype amino acid sequences of a selected native fibronectin Type 3 polypeptide or polypeptides, and (b) loop regions AB, CD, and EF having selected lengths (Bottom Loops). The Fn3 may also have loop regions BC, DE, and FG having wildtype amino acid sequences, having selected lengths, or mutagenized amino acid sequences (Top Loops).
184 Universal fibronectin type III bottom-side binding domain libraries US13504824 2010-10-27 US09139825B2 2015-09-22 Andreas Loew; Brian Edward Vash
The invention pertains to a natural-variant combinatorial library of fibronectin Type 3 domain (Fn3) polypeptides useful in screening for the presence of one or more polypeptides having a selected binding or enzymatic activity. The library polypeptides include (a) regions A, AB, B, C, CD, D, E, EF, F, and G having wildtype amino acid sequences of a selected native fibronectin Type 3 polypeptide or polypeptides, and (b) loop regions AB, CD, and EF having selected lengths (Bottom Loops). The Fn3 may also have loop regions BC, DE, and FG having wildtype amino acid sequences, having selected lengths, or mutagenized amino acid sequences (Top Loops).
185 Programmable iterated elongation: a method for manufacturing synthetic genes and combinatorial DNA and protein libraries US12308557 2007-06-19 US08962532B2 2015-02-24 Ehud Y. Shapiro; Gregory Linshiz; Tuval Ben-Yehezkel; Shai Kaplan; Rivka Adar; Ilan Gronau; Sivan Tuvi
A method for manufacturing synthetic genes and combinatorial DNA and protein libraries, termed here Divide and Conquer-DNA synthesis (D&C-DNA synthesis) method. The method can be used in a systematic and automated way to synthesize any long DNA molecule and, more generally, any combinatorial molecular library having the mathematical property of being a regular set of strings. The D&C-DNA synthesis method is an algorithm design paradigm that works by recursively breaking down a problem into two or more sub-problems of the same type. The division of long DNA sequences is done in silico. The assembly of the sequence is done in vitro. The D&C-DNA synthesis method protocol consists of a tree, in which each node represents an intermediate sequence. The internal nodes are created in elongation reactions from their daughter nodes, and the leaves are synthesized directly. After each elongation only one DNA strand passes to the next level in the tree until receiving the final product. Optionally and preferably, error correction is performed to correct any errors which may have occurred during the synthetic process.
186 Common protein surface shapes and uses therefor US12542427 2009-08-17 US08635027B2 2014-01-21 Mark Leslie Smythe; Tran Trung Tran; Darryn Bryant; Stephen Long; Peter Adams
A method of determining common three-dimensional structural features of protein surfaces is provided, as is use of representations of these common structures in molecular database searching and in designing focused molecular libraries. The method is particularly concerned with the analysis and representation of protein surfaces such as b-turns, loops and contact surfaces. In one form, the method identifies common locations and orientations of amino acid side-chains, simplified as Cα-Cβ vectors. In another form, the method identifies common regions of surface charge represented by grid points in three-dimensional space. Further provided are common three dimensional structural features of proteins that can be used to search molecular databases for the purposes of identifying molecules that match these common three dimensional structural features. The common three dimensional structural features can also be used to focus de novo molecular generation to produce libraries containing molecules that have these common three dimensional structural features. Libraries of these structurally-related molecules may then be produced for the purposes of drug discovery.
187 Construction of diverse synthetic peptide and polypeptide libraries US11864525 2007-09-28 US08131480B2 2012-03-06 Lawrence Horowitz; Ramesh Bhatt; Aaron L. Kurtzman
The present invention concerns the design and construction of diverse peptide and polypeptide libraries. In particular, the invention concerns methods of analytical database design for creating datasets using multiple relevant parameters as filters, and methods for generating sequence diversity by directed multisyntheses oligonucleotide synthesis. The present methods enable the reduction of large complex annotated databases to simpler datasets of related sequences, based upon relevant single or multiple key parameters that can be individually directly defined. The methods further enable the creation of diverse libraries based on this approach, using multisynthetic collections of discrete and degenerate oligonucleotides to capture the diverse collection of sequences, or portions thereof.
188 Method and system using systematically varied data libraries US10225564 2002-08-20 US07873477B1 2011-01-18 Claes Gustafsson; Sridhar Govindarajan; Jeremy S. Minshull; Jon E. Ness; Robin A. Emig
Methods and systems for providing biological results in the form of systematically varied libraries of sequences or as data representing sequences or physical preparations of systematically varied libraries and/or selections from systematically varied libraries.
189 Method for making polynucleotides having desired characteristics US11975638 2007-10-18 US07853410B2 2010-12-14 Sergey A. Selifonov; Willem P. C. Stemmer; Claes Gustafsson; Matthew Tobin; Stephen del Cardayre; Phillip A. Patten; Jeremy Minshull; Lorraine J. Giver
In silico nucleic acid recombination methods, related integrated systems utilizing genetic operators and libraries made by in silico shuffling methods are provided.
190 Programmable iterated elongation: a method for manufacturing synthetic genes and combinatorial dna and protein libraries US12308557 2007-06-19 US20100240538A1 2010-09-23 Ehud Y. Shapiro
A method for manufacturing synthetic genes and combinatorial DNA and protein libraries, termed here Divide and Conquer-DNA synthesis (D&C-DNA synthesis) method. The method can be used in a systematic and automated way to synthesize any long DNA molecule and, more generally, any combinatorial molecular library having the mathematical property of being a regular set of strings. The D&C-DNA synthesis method is an algorithm design paradigm that works by recursively breaking down a problem into two or more sub-problems of the same type. The division of long DNA sequences is done in silico. The assembly of the sequence is done in vitro. The D&C-DNA synthesis method protocol consists of a tree, in which each node represents an intermediate sequence. The internal nodes are created in elongation reactions from their daughter nodes, and the leaves are synthesized directly. After each elongation only one DNA strand passes to the next level in the tree until receiving the final product. Optionally and preferably, error correction is performed to correct any errors which may have occurred during the synthetic process.
191 Methods, systems, and software for identifying functional biomolecules US10379378 2003-03-03 US07783428B2 2010-08-24 Claes Gustafsson; Sridhar Govindarajan; Robin A. Emig; Richard John Fox; Ajoy K. Roy; Jeremy S. Minshull; S. Christopher Davis; Anthony R. Cox; Phillip A. Patten; Linda A. Castle; Daniel L. Siehl; Rebecca Lynne Gorton; Teddy Chen
The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.
192 Methods, systems, and software for identifying functional biomolecules US11981577 2007-10-30 US07751986B2 2010-07-06 Claes Gustafsson; Sridhar Govindarajan; Robin A. Emig; Richard John Fox; Ajoy K. Roy; Jeremy S. Minshull; S. Christopher Davis; Anthony R. Cox; Phillip A. Patten; Linda A. Castle; Daniel L. Siehl; Rebecca Lynne Gorton; Teddy Chen
The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.
193 Method and apparatus for codon determining US10232770 2002-08-30 US07702464B1 2010-04-20 Robin A. Emig; Richard John Fox; Claes Gustafsson; Sridhar Govindarajan; Jeremy S. Minshull; Guy Cavet
Computer processing methods and/or systems for minimizing and/or optimizing data strings in accordance with rules and options. Minimized data strings can represent data sequences important in certain biologic analyses and/or syntheses. In specific embodiments, a request is generated by a user at a client system and received by a server system. The server system accesses initial data indicated or provided by the client system. The server system then performs an analysis to minimize the data needed for further reactions. In specific embodiments, a server can use proprietary methods or data at the server side while protecting those proprietary methods and data from access by the client system.
194 OPTIMIZATION OF CROSSOVER POINTS FOR DIRECTED EVOLUTION US12557434 2009-09-10 US20100070192A1 2010-03-18 Emily C. Mundorff; Sridhar Govindarajan; Claes Gustafsson; Jeremy S. Minshull
Methods and devices for more efficiently engineering diversity into recombinant polypeptides and/or nucleic acids are provided herein. For example, a variety of methods of selecting and/or assessing potential crossover sites in an amino acid sequence or a nucleotide sequence are provided, as well as the resulting chimeric product sequences. These methods include, e.g., consideration of structural, functional and/or statistical data in the selection and assessment of sequences and crossover sites for use in recombination.
195 COMMON PROTEIN SURFACE SHAPES AND USES THEREFOR US12542427 2009-08-17 US20090318311A1 2009-12-24 Mark Leslie Smythe; Tran Trung Tran; Darryn Bryant; Stephen Long; Peter Adams
A method of determining common three-dimensional structural features of protein surfaces is provided, as is use of representations of these common structures in molecular database searching and in designing focused molecular libraries. The method is particularly concerned with the analysis and representation of protein surfaces such as b-turns, loops and contact surfaces. In one form, the method identifies common locations and orientations of amino acid side-chains, simplified as Cα-Cβ vectors. In another form, the method identifies common regions of surface charge represented by grid points in three-dimensional space. Further provided are common three dimensional structural features of proteins that can be used to search molecular databases for the purposes of identifying molecules that match these common three dimensional structural features. The common three dimensional structural features can also be used to focus de novo molecular generation to produce libraries containing molecules that have these common three dimensional structural features. Libraries of these structurally-related molecules may then be produced for the purposes of drug discovery.
196 CONSTRUCTION OF DIVERSE SYNTHETIC PEPTIDE AND POLYPEPTIDE LIBRARIES US11864525 2007-09-28 US20090082213A1 2009-03-26 Lawrence Horowitz; Ramesh Bhatt; Aaron L. Kurtzman
The present invention concerns the design and construction of diverse peptide and polypeptide libraries. In particular, the invention concerns methods of analytical database design for creating datasets using multiple relevant parameters as filters, and methods for generating sequence diversity by directed multisyntheses oligonucleotide synthesis. The present methods enable the reduction of large complex annotated databases to simpler datasets of related sequences, based upon relevant single or multiple key parameters that can be individually directly defined. The methods further enable the creation of diverse libraries based on this approach, using multisynthetic collections of discrete and degenerate oligonucleotides to capture the diverse collection of sequences, or portions thereof.
197 Methods for making character strings, polynucleotides and polypeptides having desired characteristics US11975638 2007-10-18 US20080050782A1 2008-02-28 Sergey Selifonov; Willem Stemmer; Claes Gustafsson; Matthew Tobin; Stephen Cardayre; Phillip Patten; Jeremy Minshull; Lorraine Giver
In silico nucleic acid recombination methods, related integrated systems utilizing genetic operators and libraries made by in silico shuffling methods are provided.
198 Methods, systems, and software for identifying functional biomolecules US11706034 2007-02-12 US20070239364A1 2007-10-11 Richard Fox
The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.
199 Methods and apparatus for preparing high-dimensional combinatorial experiments US11348873 2006-02-06 US20070214101A1 2007-09-13 Youqi Wang; Marco Falcioni; Stephen Turner; C. Ramberg
Computer-implemented methods, systems and apparatus, including computer program apparatus, provide techniques for designing a set of experiments to be performed with a set of resources. A plurality of experimental configurations are generated based on a set of parameters describing factors to be varied in the experiments and a set of constraints representing limitations on operations that can be performed with the set of resources. A set of experiments is defined based on a selected configuration. The constraints can be represented as patterns defining an application of a parameter to a set of one or more points of an experimental lattice.
200 Methods and Systems for Generating and Evaluating Peptides US11561266 2006-11-17 US20070197773A1 2007-08-23 Gregory Stephanopoulos; Kyle Jensen; Christopher Loose
A method has been developed to create databases of peptides having a desirable property, such as antimicrobial activity, based on analyzing a database of known peptides for a pattern statistically associated with an activity. One can determine a set of patterns that may be representative of a peptide having a desired characteristic or property, and evaluate a set of sequences against the set of patterns (grammars) to determine if the peptide sequence being evaluated has similar patterns to those of a peptide having the desired characteristic or property. The set of sequences being evaluated may include peptide sequences of a desired length comprising all or substantially all combinations of amino acids that conform to at least one of the set of patterns. Once the database is identified the database may be processed in a pattern recognition procedure that identifies a set of patterns that could be understood as representative of a peptide having the characteristic of interest. A set of newly generated peptides sequences may then be processed to score these new sequences against the identified patterns to correlate the patterns to the sequences and determine a degree of association or a similarity between a respective one of the new sequences and the set of identified patterns. The method is used to provide a database of sequences that are expected to have one or more desired activities, specific sequences within the database proven to have the desired activity, and the patterns or grammars used to create the database of sequences. Although described with reference to antimicrobial peptides, a database of peptides may be identified that contains peptides that have antiviral properties, wound response properties, or some other property of interest.
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