Scalable high-density peptide arrays for comprehensive health monitoring

Legutki, Joseph Barten; Zhao, Zhan; Greving, Matt; Woodbury, Neal W.; Johnston, Stephen Albert; Stafford, Phillip

doi:10.1038/ncomms5785

Cited by 103 publications

(123 citation statements)

References 41 publications

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…For the 10,000 arrays, we used Applied Microarrays (Tempe, AZ) to print 10,420 peptides onto aminosilane-coated glass slides in duplicate, creating a two-up single-use peptide microarray (4). A higher-density 330,000 array is made using lithography techniques, creating a 24-up single-use peptide microarray of 330,000 peptides per array (2). Secondary detection antibodies were purchased from Thermo-Fisher (Waltham, MA) who supplied the goat anti-human IgG (HϩL) Alexa-Fluor 555 conjugate for IgG detection, and from Jackson ImmunoResearch (West Grove, PA) who supplied the rabbit anti-human IgM Fc 5 Alexa-Fluor 647 conjugate for IgM detection.…”

Section: Methodsmentioning

confidence: 99%

“…An immunosignature provides a snapshot of many antibodies simultaneously. If immunosignature data are queried using statistical and machine learning methods, these seemingly random patterns of antibody-peptide interactions can diagnose disease, even many diseases simultaneously (2,3). However, it has become clear that healthy controls play an important role in the ability to detect disease patterns.…”

mentioning

confidence: 99%

See 1 more Smart Citation

General Assessment of Humoral Activity in Healthy Humans

Stafford

Wrapp

Johnston

2016

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

The humoral immune system is network of biological molecules designed to maintain a healthy homeostatic equilibrium. Because antibodies are an abundant and highly specific effector of immunological action, they are also an important reservoir of previous host exposures. Antibodies may play a major role in early detection of host challenge. Unfortunately, few practical methods exist for interpreting the information stored in antibody variable regions. Immunosignatures use a microarray of thousands of random sequence peptides to interrogate antibodies in a broad and unbiased fashion. The pattern of binding between antibody and peptide is reproducible. Once the system has been trained on a disease cohort, blinded samples can be reliably predicted. Although immunosignatures of both chronic and infectious disease have been extensively tested, less has been done to demonstrate how healthy immunosignatures change over time or between individuals. Here, we report the results of a study of immunosignatures of healthy persons over brief (12 h sampled once per hour), intermediate (32 days sampled once per day), and long (5 years sampled once every year) time spans. Using this information, we were also able to detect intentional and unintentional immunological perturbations in the form of a vaccine and an infection, respectively. Our findings suggest that, even with the variability inherent in healthy immunosignatures, a single person's immunosignature will remain constant over time. Over this healthy signature, vaccines and infections create subsignatures that are common across multiple people, even subsuming healthy fluctuations.

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

General Assessment of Humoral Activity in Healthy Humans

Stafford

Wrapp

Johnston

2016

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, immunological screening of peptides showing polymorphisms among T. cruzi 'types' is expected to improve the robustness of currently-available immunotyping methods [123,124]. Similar genome-wide strategies using alternative platforms/screening methods are being employed to identify immune signatures in other pathogens [125].…”

Section: Box 1 Building a Genetic System From Scratch: Cloning The Cmentioning

confidence: 99%

Neglected Tropical Diseases in the Post-Genomic Era

2015

View full text Add to dashboard Cite

“…To generate immunosignatures, researchers examined the sera of patients with one of six cancers or one of six infectious diseases (10 patients with each disease). 2 For each disease, researchers identified the top 50 most informative peptides-that is, those most able to discriminate between diseases.…”

Section: Immunosignature For Cancer and Infections What Is It?mentioning

confidence: 99%