Abstract: 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.

Abstract: Aspects of the invention relate to variant proteins and methods for designing and using the same. In some embodiments, the invention relates to methods for determining a functional variant of a protein that is restricted by one or more known legal rights, such as patent rights. Functional variants according to this invention are free of such restrictions.

Abstract: Biological sample target classification, detection and selection methods are described, together with related arrays and oligonucleotide probes.

Abstract: The present invention provides systems for developing and/or testing therapies for prenatal diseases and conditions including Down Syndrome. The present invention also provides diagnostic methods for Down Syndrome involving, in some embodiments, gene expression analyses of fetal RNA and/or detection of expression of particular genes involved in Down Syndrome. Also provided are microarrays and kits useful in prenatal diagnostic applications.

Abstract: The present patent application discloses a method of identifying or validating a compound that modulates the phosphorylation-dependent activity of a target protein or protein complex, where the target protein or protein complex activity is regulated by phosphorylation, as well as the use of identified compounds for the production of a pharmaceutical preparation especially for the treatment of cancer, insulin resistance and diabetes.

Abstract: A chromatographic device for use in multi-dimensional GC is described having a gas flow channel means having an inlet and an outlet, and including a first length of tube defining a first stage and a second length of tube defining a second stage; wherein each of the first length of tube defining a first stage and second length of tube defining a second stage is microfabricated in the plane of a planar substrate layer such that each length of tube comprises a bore defining a closed curve in cross section. A GC assembly further comprising modulator, injector and detector and a method of fabrication of device and assembly are described. A method of analysing multi-dimensional GC data is described.

Abstract: The present invention relates to co-crystals of cetuximab Fab in a complex with extracellular domain of EGFR, and structure coordinates obtained from such crystal. Such coordinates are useful for identifying mimetics that bind to the extracellular domain of EGFR. Such mimetics may for example inhibit binding of ligand to EGFR, inhibit activation of EGFR, and/or reduce proliferation of tumor cells.

Abstract: A method of selecting a set of candidate polypeptides for a sample polypeptide that includes a first refining of a collection of candidate polypeptides from differences in mass of fragments of the sample polypeptide produced by mass spectrometry and a second refining of the collection of candidate polypeptides from the absolute mass of the sample polypeptide and the absolute mass of the fragments.

Abstract: Systems, methods, and other embodiments associated with sequence matching with no more than a number E errors are disclosed. A test fragment to be located within a target sequence with at most a number E errors is received. The test fragment is broken into E+1 test sub-fragments. If one test sub-fragment is located within the target sequence with no errors; a determination is made as to whether the other test sub-fragments are located within the target sequence adjacent to the one test sub-fragment with a total of at most E errors. If the other test sub-fragments are located within the target sequence adjacent the one test sub-fragment with at most E errors, a location of the test fragment within the target sequence is returned.

Abstract: Methods and systems for assessing the probabilities of the expression of one or more traits in progeny are described.

Abstract: The present invention relates to compounds having pharmacological activity towards the 5-HT7 receptor; to a method for identifying them as 5-HT7 ligands, especially as agonists, by using a pharmacophore and a descriptor's profile filter; to pharmaceutical compositions comprising them; and to their use in therapy, in particular for the treatment and or prophylaxis of a disease in which 5-HT7 is involved, such as CNS disorders.

Abstract: A set of known protein sequences associated with an organism is identified, wherein each known protein sequence comprises a plurality of ordered residues. A set of scores associated with a set of residues of the plurality of ordered residues is identified, wherein each score indicates a frequency of a residue in sequence context. A set of unique sub-sequences of the set of known protein sequences is identified. A plurality of protein signature residues is determined based on the set of scores associated with the set of residues and the set of unique sub-sequences.

Abstract: Embodiments of the present invention provide for SAM-II riboswitches and analogs thereof, and methods for using the same. In certain embodiments of the present invention, test compounds are identified that associate with SAM-II riboswitches. In other embodiments, test compounds found to associate with SAM II can be used to increase or decrease gene expression of Gram-negative bacterial organisms.

Abstract: The severe acute respiratory syndrome virus (SARS) is a coronavirus that instigated regional epidemics in Canada and several Asian countries in 2003. The newly identified SARS coronavirus (SARS-CoV) can be transmitted among humans and cause severe or even fatal illnesses. As preventive vaccine development takes years to complete and adverse reactions have been reported to some veterinary coronaviral vaccines, anti-viral compounds must be relentlessly pursued. In this study, we analyzed the effect of aurintricarboxylic acid (ATA) on SARS-CoV replication in cell culture, and found that ATA could drastically inhibit SARS-CoV replication, with viral production being more than 1000 fold than that in the untreated control. ATA is also shown to be an effective anti-viral for several other viruses, including West Nile Virus and variola virus.

Abstract: The present invention provides a new class of peptides related to rapid replication and high human mortality, and their use in diagnosing, preventing and treating disease including vaccines and therapeutics for emerging viral diseases and methods of identifying the new class of peptides and related structures.

Abstract: The present invention relates to the field of therapeutic methods, compositions and uses thereof, that affect, directly or indirectly, the behavior of LRP receptors. These compositions and methods result in the treatment of inflammatory, immunological and metabolic conditions. More particularly, the methods and compositions of the invention are directed to the identification of small molecules, drugs and/or pharmacological agents that affect the Wnt pathway by affecting normal complex formation among various signaling receptors, the LRP5 and LRP6 receptor, and related ligands.

Abstract: The present application provides for various embodiments of methods for the analysis of high resolution melt (HRM) curve data; where statistical assay variations in melt curve data may result from system noise in an analysis system. Such system noise may arise from various sources, such as the thermal non-uniformity of a thermocycler block in a thermal cycler apparatus, a detection system, etc. Additionally, various methods for the analysis of HRM curve data may provide an identification of a sample without the need for a user inputted information.

Abstract: Disclosed herein are compositions and methods relevant to a novel Drug Metabolism Reserve Physiotype to determine the metabolic capacity of a human individual. The Drug Metabolism Reserve Physiotype allows the determination of the innate metabolic capacity of the patient relevant to antidepressant and stimulant treatment and can be predicted and diagnosed simply from a blood sample. In the disclosed method, an individual is genotyped for a plurality of polymorphisms in a gene encoding CYP2C9, a gene encoding CYP2C19 and a gene encoding CYP2D6, and the genotypes are used to produce four novel indices, which relate to the metabolic capacity of the human individual.

Abstract: A method, computer-readable medium, and system for identifying compounds from chemical libraries that can be used for the therapeutic treatment of a disease or used as lead compounds in a drug development program. In particular, information from homologous proteins is used to predict, for a target protein, molecular functions that can be used to screen libraries of compounds for individual compounds that are predicted to have high binding affinities for the target protein.

Abstract: The invention discloses means and methods for genotyping an individual head of cattle. Individual's DNA is genotyped utilising the herein defined PCR SNaP-shot protocol. The protocol comprises two PCR steps where the first step (PCR1) includes adding primers (SEQ ID No. 1-30) and/or primers extended at their 5? end with a common 10 base motif (ACGTTGGATG) to the PCR1 reaction. The second step (PCR2) includes adding extension primers (SEQ ID No. 31-45), and/or primers adjacent to corresponding specific SNPs. Further steps include producing amplicons from a PCR1 mixture comprising template DNA and the first primer set to yield PCR1 products, using PCR1 products as templates to a set of extension primers to yield PCR2 products. Size and colour separation is achieved by adding tails of different lengths to the PCR2 primers. PCR2 products are separated and the results compared with SNP profiles from the databank to obtain matching.

Abstract: Method for preparing the disaccharide ?-D-glucopyranosyl-(1?4)-2-N-acetyl-2-deoxy-?-D-glucopyranoside, comprising the step of using a mutant of a wild type glycoside hydrolase.

Abstract: The invention relates to compounds of formula 1, tautomers and salts thereof, wherein R1, R2, R3, R4, and R5 have the meanings indicated in the specification. These compounds are receptor tyrosine kinase EphB4 inhibitors useful for the treatment of angiogenesis dependent cancers and intraocular neovascular syndromes. The invention further relates to a method termed ALTA (anchor-based library tailoring) of selecting compounds from a large compound library for screening as EphB4 inhibitors by computational procedures.

Abstract: The present invention relates to methods of identifying small molecule candidate agents capable of modulating transcription factor function such that the function/expression of a target transcription factor and/or proteins downstream of this target protein comprises the screening of small molecule libraries using in silico high throughput docking for candidate small molecules/agents that are selectively identified for their ability to target and disrupt the transcription factor-DNA interface through unique transcription factor and/or DNA descriptors that are defined within a pharmacophore, and then testing/evaluating the candidate agents identified above through one or more in vitro assays for their ability to modulate transcription factor function including expression of this target protein and/or proteins that are downstream of the target transcription factor. The present invention also relates to various compounds described herein (e.g.

Abstract: The present invention relates to methods of identifying compounds that inhibit the activation between a biomolecule, pharmaceutical compositions comprising such compounds, and methods of treating and/or to reducing the risk of Bacillus anthracis and Bordetella pertussis infection by administering such pharmaceutical compositions.

Abstract: Methods and devices for diagnosing, monitoring, or determining a renal disorder in a mammal are described. In particular, methods and devices for diagnosing, monitoring, or determining a renal disorder using measured concentrations of a combination of three or more analytes in a test sample taken from the mammal are described.

Abstract: For assessing classification annotations assigned to DNA sequences stored in a reference database, the DNA sequences are grouped by species using established classification schemes. Subsequently, a measure of distance between pairs of DNA sequences is determined by aligning the respective sequences and determining the measure of distance based on a score of similarity between the aligned DNA sequences. Determined are one or more centroid sequences which have the shortest aggregate measure of distance to the other DNA sequences in the respective group (species). Assigned to the DNA sequences as a quantitative confidence level for their classification annotations is in each case the measure of distance between the respective DNA sequence and the centroid sequence. The assessment and rating of the classification annotations with these confidence levels make it possible to provide to a user a quantitative indication of the degree of representativeness of a DNA sequence for a particular species.

Abstract: The present invention relates to novel methods and products for assessing the physiological status of a subject. More particularly, the invention relates to methods of assessing the presence, risk or stage of a cancer in a subject by identifying or measuring the levels of proteins that exhibits post-stop peptides in a sample from the subject. The invention is also suitable to assess the responsiveness of a subject to a treatment, as well as to screen candidate drugs and design novel therapies. The invention may be used in any mammalian subject, particularly in human subjects.

Abstract: An analysis technique for genetic data to detect alternative spliced exons. Exon expression of similar data is analyzed using a robust regression technique to find outliers to the main regression. False outliers are detected and removed. The remaining outliers are identified as potential alternative splicing events.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: The invention relates to the FCGR2B gene and its promoter. In particular, the invention relates to FCGR2B promoters with specific nucleotides at polymorphic sites. Characterization of the nucleotides at polymorphic sites is useful for characterizing the gene and the protein and is useful for determining predisposition or susceptibility to certain diseases and infections in a subject or a population of subjects. Such characterization of the gene or protein is also useful for determining immunoresponsiveness or responsiveness to therapeutic agents in a subject or population of subjects. Thus, disclosed herein are a variety of related nucleic acids, methods and tools.

Abstract: Aspects of the present invention include probes, methods, systems that have stand alone utility and may comprise features of a drug discovery system or method. The present invention also includes pharmaceutical compositions. In more detail, the present invention provides molecular probes and methods for producing molecular probes. The present invention provides also provides systems and methods for new drug discovery. An embodiment of the present invention utilizes sets of probes of the present invention and a new approach to computational chemistry in a drug discovery method having increased focus in comparison to heretofore utilized combinatorial chemistry. The present invention also provides computer software and hardware tools useful in drug discovery systems.

Abstract: The present invention relates generally to the field of diagnostic and prognostic assays for a gynecological condition. More particularly, the present invention provides an assay for diagnosing the presence of or a risk of having a gynecological cancer or a sub-type thereof or a stage of the cancer or complications arising therefrom or other gynecological condition including an inflammatory disorder.

Abstract: The present invention provides systems, methods, and compositions for performing molecular tests. In particular, the present invention provides methods, compositions and systems for generating target sequence-linked solid supports (e.g., beads) using a solid support linked to a plurality of capture sequences and capture primers composed of a 3? target-specific portion and a 5? capture sequence portion. In certain embodiments, the target sequence linked solid support is used in sequencing methods (e.g., pyrosequencing, zero-mode waveguide type sequencing, nanopore sequencing, etc.) to determine the sequence of the target sequence (e.g., in order to detect the identity of a target nucleic acid in sample).

Abstract: Disclosed is the three-dimensional (3-D) structure of the GLP-1 receptor (GLP-1R) and methods by which the structure may be used to develop compounds that bind to, and/or modulate the GLP-1R. The technology described herein may be applied to the development of compounds that target the GLP-1R, or may be used to develop target compound that may bind to, and/or modulate the activity of the GLP-1R.

Abstract: A method of employing DNA methylation analysis for the diagnosis, prognosis, and prediction of cancer.

Abstract: The invention provides isolated peptide-methionine sulfoxide reductase nucleic acids and their encoded proteins. The present invention provides methods and compositions relating to altering peptide-methionine sulfoxide reductase levels in plants. The invention further provides recombinant expression cassettes, host cells, transgenic plants, and antibody compositions.

Abstract: The invention provides a method of predicting the size of a dog that will be attained in adulthood, comprising typing the nucleotide(s) present for a single nucleotide polymorphic (SNP) marker present in the genome of the dog at a position equivalent to position 201 in one or more of the sequences identified in Table 1, and/or at one or more positions which are in linkage disequilibrium with any one of these positions, and thereby predicting the size of the dog that will be attained in adulthood.

Abstract: The invention relates to apparatus and methods for studying intracellular rheology. The invention further relates to use of such apparatus and methods to screen for potentially therapeutic molecules that give rise to rheological effects within a cell. As one example, the disclosed ballistic intracellular nanorheology (BIN) apparatus and methods may be employed in a high-throughput screen to identify mediators or inhibitors of the cytoskeletal modifications involved in cancer metastasis.

Abstract: A crystal comprising the collagen binding domain of human GPVI is provided and defined by structural atomic coordinates. Employing computer modeling based on the crystal structure, including methods for identifying inhibitors of GPVI collagen binding activity, methods for screening libraries of compounds for potential to bind to the GPVI collagen binding domain, and methods of identifying a compound useful for the treatment of a GPVI-mediated disorder, are also provided.

Abstract: The present invention provides the identification and combination of genes that are expressed in tumors that are responsive to a given therapeutic agent and whose combined expression can be used as an index that correlates with responsiveness to that therapeutic agent. One or more of the genes of the present invention may be used as markers (or surrogate markers) to identify tumors that are likely to be successfully treated by that agent or class of agents such as hormonal or endocrine therapy or chemotherapy.

Abstract: A method for the parallel identification of one or more metabolite species within a biological sample is provided. The method comprises producing a first spectrum by subjecting the sample to a nuclear magnetic resonance analysis, the first spectrum containing individual spectral peaks representative of the one or more metabolite species contained within the sample; producing a second spectrum by subjecting the sample to a mass spectrometry analysis, the spectrum containing individual spectral peaks representative of the one or more metabolite species contained within the sample; subjecting each of the individual spectral peaks to a statistical pattern recognition analysis to identify the one or more metabolite species contained within the sample; and identifying the one or more metabolite species contained within the sample by analyzing the individual spectral peaks of the mass and nuclear magnetic resonance spectra.

Abstract: A method of estimating a grade of a prostate cancer from zinc data associated with the prostate, the zinc data being arranged gridwise in a plurality of picture-elements representing a zinc map of the prostate. The method comprises, clustering the zinc map according to zinc levels associated with the picture-elements, and estimating a cancer grade of at least one tissue region, based, at least in part, on zinc levels associated with a cluster of picture-elements representing the tissue region.

Abstract: An efficient computational method and system for predicting the folding regions and associated secondary and tertiary structures of a protein is disclosed. Methods and systems for sorting amino acid sequences based on predicted structures, as well as methods and systems for determining the presence or absence of genes in nucleic acid sequences or structural mutations in amino acid sequences are also disclosed. A method and system for the design of a protein is also disclosed.

Abstract: The invention provides materials and methods for detecting the expression of genes encoding cytochrome p450, nuclear X receptors, phase H transferases, and solute carrier family uptake pumps. The materials include sets of primers, PCR amplicons and arrays. The methods of the invention include hybridization assays. Kits and assays for the detection of the expression of the genes are also provided by the invention. In addition, the invention provides the use of the materials and methods of the invention in drug screening assays.

Abstract: The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 that is required for the coreceptors' transport to cell surfaces, resulting in less LRP5 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm.

Abstract: The present invention relates to a crystal structure of a plasma membrane proton pump type ATPase. The invention further describes method for identification of modulators of ATPases as well as uses of such modulators. Based on the provided three dimensional structure of the ATPase, various method, such as computer implemented methods may be used for identification of modulators, such putative modulators may be further analysed using in vitro and in vivo experiments to confirm there functionality. Several modulator interaction regions are described as target of regulation by ATPase modulators.

Abstract: The present invention relates to the field of therapeutic methods to screen for compounds on the basis of their ability to influence Wnt activity. The screening process is applied to both a physical library of a series of compounds and a virtual library of compounds that affect Wnt activity. In one aspect, the virtual screening process could be carried out where a permutational library of small peptides is substituted for the small organic molecules. The inventive methods may be used to empirically test for effects on Wnt activity and may also be applied to any pair of proteins involved in protein-protein interactions.

Abstract: The present invention provides methods and compositions for detecting mutations in a DNAH11 gene of a subject to diagnose primary ciliary dyskinesia (PCD) in the subject and/or to identify a subject as having an increased risk of having PCD and/or to identify a carrier of a PCD mutation.

Abstract: Disclosed is a method of predicting clinical tumor outcome by providing gene expression from a tumor sample. The method utilizes a novel genetic screen to identify genes that contribute to chemotherapeutic responsiveness, using formalin fixed paraffin embedded clinical samples of epithelial cancer, specifically serous ovarian cancer. The method is useful in predicting tumor responsiveness to chemotherapeutics, including alkylating agents, cisplatin, antimetabolites, plant alkaloids, and antitumor antibiotics. A microarray screen showed formalin fixed paraffin embedded samples can identify genes related to chemotherapeutic response with 86% efficiency.

Abstract: A method for simplification of a microbial genome or microbial nucleic acid comprising treating microbial genome or nucleic acid with an agent that modifies cytosine to form derivative microbial nucleic acid and amplifying the derivative microbial nucleic acid to produce a simplified form of the microbial genome or nucleic acid.