Abstract: The invention provides a method for determining whether a human immunodeficiency virus is resistance to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

Abstract: This invention relates, in part, to methods and compositions for determining altered susceptibility of a human immunodeficiency virus (“HIV”) to the non-nucleoside reverse transcriptase inhibitors (“NNRTIs”) efavirenz (“EFV”), nevirapine (“NVP”), and delavirdine (“DLV”), the nucleoside reverse transcriptase inhibitor AZT, and the integrase strand transfer inhibitors diketo acid 1, diketo acid 2, and L-870,810 by detecting the presence of a mutation or combinations of mutations in the gene encoding HIV reverse transcriptase that are associated with altered susceptibility to the anti-HIV drugs.

Abstract: The invention provides a method for determining whether a human immunodeficiency virus is resistance to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

Abstract: The invention provides a method for determining whether a human immunodeficiency virus is likely to be have enhanced ability to enter a cell expressing CD4 and CXCR4 relative to a reference HIV. In certain aspects, the methods comprise detecting one or more amino acids in an envelope protein of the HIV associated with enhanced ability to enter CD4- and CXCR4-expressing cells and determining that the HIV's ability to enter such cells is enhanced relative to a reference HIV, e.g., an HIV that does not comprise such amino acid(s).

Abstract: This invention relates to methods for determining hypersusceptibility of HIV-1 viruses to non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the viral genotypes. The methods generally comprise detecting, in a gene encoding reverse transcriptase of the HIV-1, the presence of a mutation at codon 65, 69, or 74 alone or in combination with one or more mutations at certain other codons. Combinations of mutations associated with hypersusceptibility to NNRTIs are also disclosed.

Abstract: The invention provides methods and kits for detecting and/or measuring receptor homodimers on a cell surface membrane. In one aspect, the methods employ pairs of probes comprising binding compounds and a cleaving probe, such that at least one binding compound binds specifically to the same epitope of a membrane-bound analyte as the cleaving probe. The binding compound includes one or more molecular tags attached through a cleavable linkage, and the cleaving probe includes a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to a homodimer of a cell surface molecules results in release of molecular tags from the binding compounds, providing a measure of formation of the homodimeric complex.

Abstract: Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.

Abstract: This invention relates, in part, to methods and compositions for determining altered susceptibility of a human immunodeficiency virus (“HIV”) to the non-nucleoside reverse transcriptase inhibitors (“NNRTIs”) efavirenz (“EFV”), nevirapine (“NVP”), and delavirdine (“DLV”), the nucleoside reverse transcriptase inhibitor AZT, and the integrase strand transfer inhibitors diketo acid 1, diketo acid 2, and L-870,810 by detecting the presence of a mutation or combinations of mutations in the gene encoding HIV reverse transcriptase that are associated with altered susceptibility to the anti-HIV drugs.

Abstract: This invention relates to methods for determining hypersusceptibility of HIV-1 viruses to non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the viral genotypes. The methods generally comprise detecting, in a gene encoding reverse transcriptase of the HIV-1, the presence of a mutation at codon 65, 69, or 74 alone or in combination with one or more mutations at certain other codons. Combinations of mutation associated with hypersusceptibility to NNRTIs are also disclosed.

Abstract: Methods, compositions and kits are disclosed for determining one or more target polypeptides in a sample where the target polypeptides have undergone a post-translational modification.

Abstract: The invention provides a method for determining whether a human immunodeficiency virus is likely to be have enhanced ability to enter a cell expressing CD4 and CXCR4 relative to a reference HIV. In certain aspects, the methods comprise detecting one or more amino acid in an envelope protein of the HIV associated with enhanced ability to enter CD4- and CXCR4-expressing cells and determining that the HIVs ability to enter such cells is enhanced relative to a reference HIV, e.g., an HIV that does not comprise such amino acid(s).

Abstract: This invention relates, in part, to methods and compositions for determining altered susceptibility of a human immunodeficiency virus (“HIV”) to the non-nucleoside reverse transcriptase inhibitors (“NNRTIs”) efavirenz (“EFV”), nevirapine (“NVP”), and delavirdine (“DLV”), the nucleoside reverse transcriptase inhibitor AZT, and the integrase strand transfer inhibitors diketo acid 1, diketo acid 2, and L-870,810 by detecting the presence of a mutation or combinations of mutations in the gene encoding HIV reverse transcriptase that are associated with altered susceptibility to the anti-HIV drugs.

Abstract: The present invention provides an approach for developing an algorithm for determining the effectiveness of anti-viral drugs based on a comprehensive analysis of paired phenotypic and genotypic data guided by phenotypic clinical cut-offs. In one aspect, the algorithm allows one to provide a patient with effective treatment. It helps predict whether an infected individual will respond to treatment with an anti-viral compound, thereby allowing an effective treatment regimen to be designed without subjecting the patient to unnecessary side effects. Also, by avoiding the administration of ineffective drugs, considerable time and money is saved.

Abstract: The present invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced

Abstract: A microfluidic analytical apparatus (10) comprising a microfluidic card pairing (12) with a corresponding circuit card (14) and the circuit card pairing (12) with corresponding conductive fingers (16). The microfluidic card (12) has a plurality of channels (32) and ports (54) on a top surface of the card in a desired configuration, the ports (54) in fluid communication with the channels (32). The circuit card (14) has a plurality of conductive pins (60) projecting from a bottom surface of the card and having a configuration that corresponds to the particular configuration of the ports (54) of the microfluidic card (12) that is paired with. The circuit card (14) is received within a holder (20) that provides that provides multiple functions.

Abstract: Families of compositions are provided as labels, referred to as eTag reporters for attaching to polymeric compounds and assaying based on release of the eTag reporters from the polymeric compound and separation and detection. For oligonucleotides, the eTag reporters are synthesized at the end of the oligonucleotide by using phosphite or phosphate chemistry, whereby mass-modifying regions, charge-modifying regions and detectable regions are added sequentially to produce the eTag labeled reporters. By using small building blocks and varying their combination large numbers of different eTag reporters can be readily produced attached to a binding compound specific for the target compound of interest for identification. Protocols are used that release the eTag reporter when the target compound is present in the sample.

Abstract: The present invention provides methods and devices for predicting whether an HIV-I is likely to have a reduced susceptibility to an antiviral drug based on the HIV-I's genotype. In one aspect, the invention provides methods comprising determining whether a mutation or combination of mutations associated with altered susceptibility to protease inhibitors are present, as disclosed herein, thereby assessing the effectiveness of tipranavir therapy in the HIV-infected subject. Computer implemented methods comprising determining HIV-I's altered susceptibility are provided.

Abstract: The invention provides a method for determining whether a human immunodeficiency virus is likely to be have enhanced ability to enter a cell expressing CD4 and CXCR4 relative to a reference HIV. In certain aspects, the methods comprise detecting one or more amino acid in an envelope protein of the HIV associated with enhanced ability to enter CD4- and CXCR4-expressing cells and determining that the HIVs ability to enter such cells is enhanced relative to a reference HIV, e.g., an HIV that does not comprise such amino acid(s).

Abstract: The invention is directed to a new class of biomarker in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of ErbB cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment.

Abstract: The invention is directed to a new class of biomarker in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of ErbB cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment.