Biology subjects

Burns, J. C.

Publications and source records attributed to Burns, J. C..

3 recordsLinked to original sources

bioRxiv2025

Minimal Correlation but Complementary Diagnostic Utility for Plasma Cell-free RNA and Proteins

Proteins and RNA circulate in plasma and can offer insights into human physiology. Yet, despite their clinical importance, direct comparisons between these analytes remain unexplored. Here, we measured and compared plasma cell-free RNA (cfRNA) and protein levels for 263 children diagnosed with inflammatory diseases by RNA-sequencing (n=155) and SomaScan proteomics (n=171). Remarkably, cfRNA and protein levels were largely uncorrelated across samples (feature-by-sample r=0.052; median feature-level r=0.009). Nonetheless, machine learning models based on either modality distinguished Kawasaki Disease (KD) from Multisystem Inflammatory Syndrome in Children (MIS-C) with similar high accuracy (median AUC > 0.93). Analysis of KD subtypes revealed distinct cfRNA and protein signatures, with one group showing molecular similarity to MIS-C. These findings underscore the complementary nature of cfRNA and protein profiling and highlight the utility of integrating multiple blood analytes to improve disease classification and deepen our understanding of complex inflammatory conditions.

genomics↗

bioRxiv2022

Autoantibody discovery across monogenic, acquired, and COVID19-associated autoimmunity with scalable PhIP-Seq

Phage Immunoprecipitation-Sequencing (PhIP-Seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-Seq for autoantigen discovery, including our previous work (Vazquez et al. 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki Disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), and finally, mild and severe forms of COVID19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as PDYN in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in 2 patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-Seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID19, including the endosomal protein EEA1. Together, scaled PhIP-Seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.

immunology↗

bioRxiv2021

An AI-guided invariant signature places MIS-C with Kawasaki disease in a continuum of host immune responses

A significant surge in cases of multisystem inflammatory syndrome in children (MIS-C, also called Pediatric Inflammatory Multisystem Syndrome - PIMS) has been observed amidst the COVID-19 pandemic. MIS-C shares many clinical features with Kawasaki disease (KD), although clinical course and outcomes are divergent. We analyzed whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues from these patients using a computational toolbox of two gene signatures, i.e., the 166-gene viral pandemic (ViP) signature, and its 20-gene severe (s)ViP subset that were developed in the context of SARS-CoV-2 infection and a 13-transcript signature previously demonstrated to be diagnostic for KD. Our analyses revealed that KD and MIS-C are on the same continuum of the host immune response as COVID-19. While both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures also revealed unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.

immunology↗