Methods and compositions for assessing antibody specificities
Inventors
Daugherty, Patrick Sean • Kamath, Kathryn Vinaya Louise • Reifert, Jack Ryan
Assignees
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Publication Number
US-10871494-B2
Publication Date
2020-12-22
Expiration Date
Abstract
The present invention provides compositions and methods that can be used to determine a peptide signature for an antibody repertoire in a sample comprising multiple antibodies. The method can be used to characterize a phenotype in a sample, such as providing a diagnosis, prognosis or theranosis of a medical condition.
Core Innovation
The invention provides an array comprising an array surface and at least five peptide probes. Each peptide probe extends from the array surface and includes a binding motif selected from a specified set of sequence motifs, including FxWN[VI]P (SEQ ID NO: 616), [FW][LM]EXAH (SEQ ID NO: 617), KxMSxFV (SEQ ID NO: 619), WP[TA]GR (SEQ ID NO: 624), KNWPx[GF] (SEQ ID NO: 625), KxxP[LI]FA (SEQ ID NO: 626), Kx[IM][VN]xWA (SEQ ID NO: 630), KGx[SA]HxF (SEQ ID NO: 636), KGxVxF[AS] (SEQ ID NO: 637), and [IV]xHxTID (SEQ ID NO: 638).
The patent describes using antibody-containing biological samples to determine probe-to-antibody binding. The workflow includes contacting the array with a subject’s antibody-containing biological sample, incubating to allow binding, and measuring the probe-to-antibody binding.
The disclosed approach is positioned for serological diagnosis and phenotype characterization, including diagnosis/prognosis/theranosis, using peptide motif discovery and enrichment-threshold based panel scoring. The document reports motif panels for multiple diseases/infections and compares motif-discovery approaches by sensitivity and specificity outcomes, including z-score based panel scoring.
Claims Coverage
The provided claim context identifies one independent array claim. One inventive feature is explicitly provided.
Motif-defined peptide-probe array
An array comprising an array surface and at least five peptide probes, wherein each of the at least five peptide probes comprises a binding motif selected from the group consisting of FxWN[VI]P (SEQ ID NO: 616), [FW][LM]EXAH (SEQ ID NO: 617), KxMSxFV (SEQ ID NO: 619), WP[TA]GR (SEQ ID NO: 624), KNWPx[GF] (SEQ ID NO: 625), KxxP[LI]FA (SEQ ID NO: 626), Kx[IM][VN]xWA (SEQ ID NO: 630), KGx[SA]HxF (SEQ ID NO: 636), KGxVxF[AS] (SEQ ID NO: 637), and [IV]xHxTID (SEQ ID NO: 638), wherein the at least five peptide probes extend from the array surface.
The explicitly provided independent claim describes a motif-defined array in which at least five peptide probes extend from an array surface and each contains a binding motif selected from the specified set of sequence motifs.
Stated Advantages
Diagnostic performance is computed using quantitative scoring based on z-scores and threshold-style constraints such as sensitivity and specificity.
The document reports motif-discovery approaches compared by sensitivity and specificity outcomes.
Documented Applications
Serological diagnosis of acute infections using peptide motif panels, including acute infections across diverse pathogens such as Toxoplasma gondii, Taenia solium/cysticercosis, EBV, Zika, HIV, Sjogren’s syndrome autoimmunity, CMV, Rhinovirus, Streptococcus, Haemophilus influenza, Leishmania, Babesia microti, Ehrlichia, and Anaplasma.
Phenotype characterization, including diagnosis/prognosis/theranosis.
Motif panels for multiple diseases/infections.
Kits and reagents used to support array-based binding measurement and analysis.
Diagnosis of Anaplasma phagocytophilum infection by contacting an array of at least five peptide probes with a subject’s antibody-containing biological sample, incubating to allow binding, and measuring probe-to-antibody binding.
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