Arizona State University

Harvard College

Mayo Foundation for Medical Education and Research

Dana-farber-cancer Institute Inc.

Arizona Board of Regents, a Body Corporate

The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of Illinois

The Brigham and Women's Hospital, Inc.

University of Florida Research Foundation, Incorporated

Benaroya Research Institute at Virginia Mason

National Institutes of Health

Engineering Arts LLC

Joshua LaBaer

Garrick Wallstrom

Jin Park

Karen Anderson

Ji Qiu

Niroshan Ramachandran

Jie Wang

Vel Murugan

Rosa Krajmalnik-Brown

Jia Guo

Dae-Wook Kang

Sahar Sibani

Mitch Magee

Bharath Takulapalli

Benjamin Katchman

Daniel Cramer

Brian Kay

Douglas Faigel

Kevin Gorman

Zehra Ilhan

Albert Y Lau

Kristin Gillis

Merica Vorachitti

Rahul Pannala

Stuart Lindsay

John C Chaput

Mark A Atkinson

Peter Jan Wiktor

Jonine Figueroa

Clive Henry Wasserfall

Desmond A Schatz

Justin Saul

Sujay Sau

Manuel Fuentes Garcia

Ji Qui

Xiaofang Bian

Jane Buckner

Zehra IIhan

Kailash Karthikeyan

Gerald Nepom

Haoyu Wang

Jonathan Leighton

Shabana Pasha

Fernanda Festa

Femina Rauf

Al Brunner

Peter Kahn

Karen Sue Anderson

Provided herein are methods for multiplexed in situ analysis of biomolecules in a tissue. In particular, provided herein are methods for multiplexed single-cell in situ protein and nucleic acid profiling in fixed or fresh tissues, that allows the investigation of the different cell compositions and their spatial organizations in intact tissues through consecutive cycles of probe hybridization, fluorescence imaging, and signal removal.

Methods and systems for sensitive and multiplexed analysis of biological samples using high-performance cleavable, detectably-labeled tyramide

Provided herein are methods and systems for sensitive and multiplexed in situ analysis of samples such as biological samples using cleavable fluorescent streptavidin. In particular, provided herein are methods for multiplexed single-cell in situ biomolecule profiling in samples, including fixed or fresh tissues, and also allows the investigation of the different cell compositions and their spatial organizations in intact tissues through consecutive cycles of probe hybridization, fluorescence imaging, and signal removal.

Methods and systems for sensitive and multiplexed analysis of biological samples using cleavable fluorescent streptavidin and anti-hapten antibodies

Compositions and methods for detection of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. Patient samples known or suspected of containing ACPAs were probed against citrullinated proteins, and antibody responses to 190 citrullinated proteins in 20 RA patients were investigated. Unique antibody reactivity patterns in both clinical anti-cyclic citrullinated peptide assay positive (CCP+) and negative (CCP−) RA patients were observed. At individual antigen levels, six novel antibody/antigen complexes were discovered and validated against specific citrullinated antigens (Myelin Basic Protein (MBP), osteopontin (SPP1), flap endonuclease (FENI), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. Identification of immune-dominant epitope(s) for citrullinated MBP was also performed. The identified biomarkers have high specificity, especially MBP.

Identification and medical applications of anti-citrullinated-protein antibodies in rheumatoid arthritis

Compositions and methods relating to a panel of antigen biomarkers for the early detection of ovarian cancer. The compositions and methods encompass antigen biomarkers coupled to a substrate, with the biomarkers being selected from the group consisting of one or more of ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3.

Autoantibody biomarkers for the early detection of ovarian cancer

Methods and compositions for multiplexed protein-protein interaction profiling (e.g., immunoprofiling), based on nucleic acid tagging of polypeptides (e.g., by RNA display) are described. In some embodiments the described compositions and methods utilize a library of prey polypeptide targets linked to prey RNAs encoding them, and a population of bait polypeptides, e.g., a mixture of antibodies, that bind to one or more of the prey polypeptide targets and are used to isolate and identify the bound prey polypeptide targets by amplification of their associated prey RNAs and sequencing of the corresponding cDNAs. In other embodiments the prey polypeptide targets are linked to DNA Bar Codes, which serve as unique identifiers of the tagged polypeptide.

Nucleic acid-tagged compositions and methods for multiplexed protein-protein interaction profiling

The present disclosure provides for characterization of normal flora and identifying biomarkers in the gut of healthy, neurotypical subjects. Aspect of the disclosure provide for the characterization of the gut microbiome in ADS subjects, characterized by reduced richness and significant loss of the '-like enterotype' compared to neurotypical subjects. The relative abundance of generaandare significantly lower in autistic children than in neurotypical children. Further,, is one of the three main classifiers for the human enterotypes, along with Bacteroides and. These three core genera are among main contributors in the principle component analysis. ‘-like enterotype’ was absent in the autistic group, while neurotypical samples showed an even distribution among the three enterotypes. The present disclosure provides for an understanding the association between gut microbiota, health, and disease states, and provides for potential diagnostic and therapeutic targets.

Microbiome markers and therapies for autism spectrum disorders

Cancer patients make antibodies to tumor-derived proteins that are potential biomarkers for early detection. Twenty-eight antigens have been identified as potential biomarkers for the early detection of basal-like breast cancer (Tables 1, 2). Also, a 13-AAb classifier has been developed that differentiate patients with BLBC from healthy controls with 33% sensitivity at 98% specificity (Table 3).

Plasma autoantibody biomarkers for basal like breast cancer

Provided herein are affinity reagents having affinity for particular target, each reagent having a unique DNA barcode, and methods for using the same to measure the abundance of targets in a sample. In particular, methods are provided in which unique barcodes linked to affinity reagents are contacted to a sample to bind antigens if present in said sample. In cases in which the affinity reagents are antibodies and the targets are antigens, antibodies that are bound to their target antigens can be separated from unbound antibodies and the DNA barcode associated with the affinity reagent is amplified, such as with a PCR reaction. In some cases, amplified barcode DNA is subjected to DNA sequencing as a measure of the levels of the target protein in the sample.

Methods for targeted protein quantification by bar-coding affinity reagent with unique DNA sequences

Methods for screening of affinity reagents for many target proteins of interest simultaneously. Arrayed targets (e.g., peptide, protein, RNA, cell, etc.) are used in affinity selection experiments to reduce the amount of target needed and to improve the throughput of discovering recombinant affinity reagents to a large collection of targets.

Generating recombinant affinity reagents with arrayed targets

Provided herein are qPCR-based methods for quantitatively detecting and differentiating between live and dead pathogenic bacteria such as carbapenem-resistant Enterobacteriaceae (CRE). Also provided herein are simple, fast, and reliable genomic DNA extraction methods with improved efficiency.

Methods for detection and quantification of infectious carbapenem resistant enterobacteriaceae (CRE)

Described herein are biosensor microarrays comprising detector polypeptide monolayers substantially free of contaminants. Also provided are methods for generation of such biosensor microarrays by capture of polypeptides by arrays comprising capture moieties and associated sensors.

Biosensor microarray compositions and methods

Provided herein are methods and systems for sensitive and multiplexed in situ analysis of samples such as biological samples using cleavable hapten linked targeting agents and cleavable detectably-labeled hapten-binding agents. In particular, provided herein are methods for multiplexed single-cell in situ biomolecule profiling in samples, including fixed or fresh tissues, and also allows the investigation of the different cell compositions and their spatial organizations in intact tissues through consecutive cycles of probe hybridization, fluorescence imaging, and signal removal.

The present invention provides reagents and methods for breast cancer detection.

Biomarkers for the early detection of breast cancer

Type 1 diabetes (T1D) patients make antibodies to self-proteins that are potential biomarkers for early detection and risk prediction. We have identified seventeen antigens as biomarkers for early diagnosis and risk prediction of T1D, including the antigens MLH1, MTIF3, PPIL2, NUP50, TOX4, FIGN, C9orf142, ZNF280D, HES1, QRFPR, CTRC, SNX6, SYTL4, ELA2A, IGRP, PAX6, and HMGN3.

Methods for diagnosis of type 1 diabetes

Growing community of inventors

Chandler, AZ, United States of America

Joshua LaBaer