Proteomics Investigation of Diverse Serological Patterns in COVID-19

Liang, Xiao; Sun, Rui; Wang, Jing; Zhou, Kai; Li, Jun; Chen, Shiyong; Lyu, Mengge; Li, Sainan; Xue, Zhangzhi; Shi, Yingqiu; Xie, Yuting; Zhang, Qiushi; Yi, Xiao; Pan, Juan; Wang, Donglian; Xu, Jiaqin; Zhu, Hongying; Zhu, Guangjun; Zhu, Jiansheng; Zhu, Yi; Zheng, Yufen; Shen, Bo; Guo, Tiannan

doi:10.1016/j.mcpro.2023.100493

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…Serum proteomic analyses also detected increased FH and FHR-5 levels in patients infected with SARS-CoV-2 compared to healthy controls (226-228). FHR-2 elevation in serum was also described (229). In a recent study, serum levels of all FH family proteins in COVID-19 patients and controls were quantified using a targeted mass spectrometry approach; while no elevation in FH level was found, the serum levels of all other FH protein family members were increased, with FHR-2 and FHR-5 showing the highest elevation in severe COVID cases compared to controls (230).…”

Section: Interaction Of Fh Family Proteins With Microbesmentioning

confidence: 92%

The human factor H protein family – an update

Sándor,

Schneider,

Matola

et al. 2024

Front. Immunol.

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Complement is an ancient and complex network of the immune system and, as such, it plays vital physiological roles, but it is also involved in numerous pathological processes. The proper regulation of the complement system is important to allow its sufficient and targeted activity without deleterious side-effects. Factor H is a major complement regulator, and together with its splice variant factor H-like protein 1 and the five human factor H-related (FHR) proteins, they have been linked to various diseases. The role of factor H in inhibiting complement activation is well studied, but the function of the FHRs is less characterized. Current evidence supports the main role of the FHRs as enhancers of complement activation and opsonization, i.e., counter-balancing the inhibitory effect of factor H. FHRs emerge as soluble pattern recognition molecules and positive regulators of the complement system. In addition, factor H and some of the FHR proteins were shown to modulate the activity of immune cells, a non-canonical function outside the complement cascade. Recent efforts have intensified to study factor H and the FHRs and develop new tools for the distinction, quantification and functional characterization of members of this protein family. Here, we provide an update and overview on the versatile roles of factor H family proteins, what we know about their biological functions in healthy conditions and in diseases.

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Section: Interaction Of Fh Family Proteins With Microbesmentioning

confidence: 92%

The human factor H protein family – an update

Sándor,

Schneider,

Matola

et al. 2024

Front. Immunol.

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“…Recently, immunoaffinity proteomics was demonstrated as a conceptually novel platform for serological diagnostics [ 10 , 144 , 145 ]. Simple assay design and targeted proteomics measurements provided high sensitivity (1 ng/mL), high reproducibility (CV < 10%), and relatively high throughput (~ 100 samples/day) [ 10 ].…”

Section: Main Textmentioning

confidence: 99%

Redefining serological diagnostics with immunoaffinity proteomics

Walter,

Eludin,

Drabovich

2023

Clin Proteom

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Serological diagnostics is generally defined as the detection of specific human immunoglobulins developed against viral, bacterial, or parasitic diseases. Serological tests facilitate the detection of past infections, evaluate immune status, and provide prognostic information. Serological assays were traditionally implemented as indirect immunoassays, and their design has not changed for decades. The advantages of straightforward setup and manufacturing, analytical sensitivity and specificity, affordability, and high-throughput measurements were accompanied by limitations such as semi-quantitative measurements, lack of universal reference standards, potential cross-reactivity, and challenges with multiplexing the complete panel of human immunoglobulin isotypes and subclasses. Redesign of conventional serological tests to include multiplex quantification of immunoglobulin isotypes and subclasses, utilize universal reference standards, and minimize cross-reactivity and non-specific binding will facilitate the development of assays with higher diagnostic specificity. Improved serological assays with higher diagnostic specificity will enable screenings of asymptomatic populations and may provide earlier detection of infectious diseases, autoimmune disorders, and cancer. In this review, we present the major clinical needs for serological diagnostics, overview conventional immunoassay detection techniques, present the emerging immunoassay detection technologies, and discuss in detail the advantages and limitations of mass spectrometry and immunoaffinity proteomics for serological diagnostics. Finally, we explore the design of novel immunoaffinity-proteomic assays to evaluate cell-mediated immunity and advance the sequencing of clinically relevant immunoglobulins.

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“…Plasma proteomics have provided significant biological insights into the immunopathology of severe COVID-19, which is characterized by the inflammatory “cytokine storm”, Acute Respiratory Distress Syndrome (ARDS), PANoptosis-induced cell death, and multiorgan failure (Diamond and Kanneganti, 2022). Plasma proteomics has also been explored in long-COVID-19 syndromes and vaccine response variations (Liang et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…PANoptosis-induced cell death, and multiorgan failure (Diamond and Kanneganti, 2022). Plasma proteomics has also been explored in long-COVID-19 syndromes and vaccine response variations (Liang et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19

Gavriilidis,

Vasileiou,

Dimitsaki

et al. 2024

Preprint

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MotivationComputational analyses of plasma proteomics provide translational insights into complex diseases such as COVID-19 by revealing molecules, cellular phenotypes, and signaling patterns that contribute to unfavorable clinical outcomes. Currentin silicoapproaches dovetail differential expression, biostatistics, and machine learning, but often overlook nonlinear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking.ResultsWe introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically-informed sparse deep learning model to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests co-expression and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19.Availability and ImplementationAPNet’s R, Python scripts and Cytoscape methodologies are available athttps://github.com/BiodataAnalysisGroup/APNetContactggeorav@certh.grSupplementary informationSupplementary information can be accessed in Zenodo (10.5281/zenodo.10438830).

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Proteomics Investigation of Diverse Serological Patterns in COVID-19

Cited by 5 publications

References 43 publications

The human factor H protein family – an update

The human factor H protein family – an update

Redefining serological diagnostics with immunoaffinity proteomics

APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19

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