Phage ImmunoPrecipitation Sequencing (PhIP-Seq): The Promise of High Throughput Serology

Tiu, Charles; Zhu, Feng; Wang, Lin‐Fa; Alwis, Ruklanthi de

doi:10.3390/pathogens11050568

Cited by 12 publications

(10 citation statements)

References 51 publications

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“…Various methods, such as peptide and cDNA arrays [ 42 , 43 ], phage display [ 44 ], fluid-phase immunoassays [ 43 ], and antigen microarrays [ 45 ], have been used in discovering autoantigens. Among these, the phage display involving the T7 bacteriophage has proven to be a fast and high-throughput proteomic screening platform [ 24 , 46 , 47 ]. This approach has been widely used to screen antibodies for reactivity to viruses, autoantigens (including the neoantigens in tumor settings), microbial toxins and virulence factors [ 48 ], and allergens in basic and clinical research [ 23 , 49 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…This notion is supported by the fact that the detection of autoantibodies does not necessarily mean that autoimmune disease ensues [ 80 , 81 , 82 ]. In fact, a theme is developing that the determination of autoantibodies in combination with other multi-analyte ‘omic’ profiles may be helpful for predicting the diseases as well as disease intervention or prevention strategies [ 47 , 53 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

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PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis

Rasquinha

Lasrado

Petro-Turnquist

et al. 2022

Biology

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Enteroviruses such as group B coxsackieviruses (CVB) are commonly suspected as causes of myocarditis that can lead to dilated cardiomyopathy (DCM), and the mouse model of CVB3 myocarditis is routinely used to understand DCM pathogenesis. Mechanistically, autoimmunity is suspected due to the presence of autoantibodies for select antigens. However, their role continues to be enigmatic, which also raises the question of whether the breadth of autoantibodies is sufficiently characterized. Here, we attempted to comprehensively analyze the autoantibody repertoire using Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a versatile and high-throughput platform, in the mouse model of CVB3 myocarditis. First, PhIP-Seq analysis using the VirScan library revealed antibody reactivity only to CVB3 in the infected group but not in controls, thus validating the technique in this model. Second, using the mouse peptide library, we detected autoantibodies to 32 peptides from 25 proteins in infected animals that are ubiquitously expressed and have not been previously reported. Third, by using ELISA as a secondary assay, we confirmed antibody reactivity in sera from CVB3-infected animals to cytochrome c oxidase assembly factor 4 homolog (COA4) and phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), indicating the specificity of antibody detection by PhIP-Seq technology. Fourth, we noted similar antibody reactivity patterns in CVB3 and CVB4 infections, suggesting that the COA4- and PIK3AP1-reactive antibodies could be common to multiple CVB infections. The specificity of the autoantibodies was affirmed with influenza-infected animals that showed no reactivity to any of the antigens tested. Taken together, our data suggest that the autoantibodies identified by PhIP-Seq may have relevance to CVB pathogenesis, with a possibility that similar reactivity could be expected in human DCM patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis

Rasquinha

Lasrado

Petro-Turnquist

et al. 2022

Biology

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“…The newest cutting-edge multiplex serology assay with the potential to revolutionize sero-surveillance of infectious diseases is the phage-immunoprecipitation assay (PhIP-Seq) [ 41 , 75 ]. The PhIP-Seq technology allows serology to be “megaplexed”, i.e., the detection of up to a million different pathogen proteins.…”

Section: Current Methods New Technologies and Future Directionsmentioning

confidence: 99%

Serology as a Tool to Assess Infectious Disease Landscapes and Guide Public Health Policy

Haselbeck

Prifti

et al. 2022

Pathogens

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Understanding the local burden and epidemiology of infectious diseases is crucial to guide public health policy and prioritize interventions. Typically, infectious disease surveillance relies on capturing clinical cases within a healthcare system, classifying cases by etiology and enumerating cases over a period of time. Disease burden is often then extrapolated to the general population. Serology (i.e., examining serum for the presence of pathogen-specific antibodies) has long been used to inform about individuals past exposure and immunity to specific pathogens. However, it has been underutilized as a tool to evaluate the infectious disease burden landscape at the population level and guide public health decisions. In this review, we outline how serology provides a powerful tool to complement case-based surveillance for determining disease burden and epidemiology of infectious diseases, highlighting its benefits and limitations. We describe the current serology-based technologies and illustrate their use with examples from both the pre- and post- COVID-19-pandemic context. In particular, we review the challenges to and opportunities in implementing serological surveillance in low- and middle-income countries (LMICs), which bear the brunt of the global infectious disease burden. Finally, we discuss the relevance of serology data for public health decision-making and describe scenarios in which this data could be used, either independently or in conjunction with case-based surveillance. We conclude that public health systems would greatly benefit from the inclusion of serology to supplement and strengthen existing case-based infectious disease surveillance strategies.

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“…Both data sets include a comprehensive report of past or ongoing exposures to each of the >200 viruses included in the original human 1 https://matsonslab.com virome library. For a detailed description of the VirScan library, see other sources (26,(31)(32)(33)40). Briefly, protein sequences from whole genomes of 206 virus species and 1,000 virus strains were divided into overlapping 56mer peptide fragments and synthesized commercially as oligo pools.…”

Section: Virscanmentioning

confidence: 99%

Applications of VirScan to broad serological profiling of bat reservoirs for emerging zoonoses

Ruhs,

Chia,

Foo

et al. 2023

Front. Public Health

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IntroductionBats are important providers of ecosystem services such as pollination, seed dispersal, and insect control but also act as natural reservoirs for virulent zoonotic viruses. Bats host multiple viruses that cause life-threatening pathology in other animals and humans but, themselves, experience limited pathological disease from infection. Despite bats’ importance as reservoirs for several zoonotic viruses, we know little about the broader viral diversity that they host. Bat virus surveillance efforts are challenged by difficulties of field capture and the limited scope of targeted PCR- or ELISA-based molecular and serological detection. Additionally, virus shedding is often transient, thus also limiting insights gained from nucleic acid testing of field specimens. Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a broad serological tool used previously to comprehensively profile viral exposure history in humans, offers an exciting prospect for viral surveillance efforts in wildlife, including bats.MethodsHere, for the first time, we apply PhIP-Seq technology to bat serum, using a viral peptide library originally designed to simultaneously assay exposures to the entire human virome.ResultsUsing VirScan, we identified past exposures to 57 viral genera—including betacoronaviruses, henipaviruses, lyssaviruses, and filoviruses—in semi-captive Pteropus alecto and to nine viral genera in captive Eonycteris spelaea. Consistent with results from humans, we find that both total peptide hits (the number of enriched viral peptides in our library) and the corresponding number of inferred past virus exposures in bat hosts were correlated with poor bat body condition scores and increased with age. High and low body condition scores were associated with either seropositive or seronegative status for different viruses, though in general, virus-specific age-seroprevalence curves defied assumptions of lifelong immunizing infection, suggesting that many bat viruses may circulate via complex transmission dynamics.DiscussionOverall, our work emphasizes the utility of applying biomedical tools, like PhIP-Seq, first developed for humans to viral surveillance efforts in wildlife, while highlighting opportunities for taxon-specific improvements.

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Phage ImmunoPrecipitation Sequencing (PhIP-Seq): The Promise of High Throughput Serology

Cited by 12 publications

References 51 publications

PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis

PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis

Serology as a Tool to Assess Infectious Disease Landscapes and Guide Public Health Policy

Applications of VirScan to broad serological profiling of bat reservoirs for emerging zoonoses

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