Technology

Applications

Our technologies have applications within a broad range of research fields, below are some examples of recent publications.

Inflammation

How to measure inflammation?

BioXpedia offers bioanalytical service for profiling of inflammatory markers on DNA, RNA, miRNA and protein level. Our laboratory analyses support projects from large-scale biomarker discovery to low-plex and single-assay quantification.

Inflammatory processes are involved in a wealth of diseases and pathological conditions, thus there is an enormous clinical interest in specific and sensitive analytical methods to quantify cytokines and chemokines.

Bioanalytical technologies we use to measure inflammatory markers

Immuno-PCR from Olink Proteomics

  • Panel of 92 proteins associated to e.g. inflammation, immune-response, immuno-oncology

Multiplex immuno-assay from Meso Scale Discovery®

  • Quantification of proteins associated to proinflammatory processes, immunology, neuro-inflammation, immunogenecity

Digital barcode detection from NanoString Technologies

  • Expression profile of 200-770 genes associated to inflammation, immuno-oncology, immunology

Real-time quantitative PCR from Fluidigm Biomark

  • Flexible platform for gene expression, SNP genotyping and miRNA profiling, where you select the specimens and assays that you would like to measure.

 

What is inflammation?

Inflammation is the primary response of the immune system against infection and foreign substances such as bacteria and viruses. When inflammation occurs cytokines from the white blood cells are released into the blood or the affected tissues to protect and heal the body.

Inflammation is a biological process of key importance for biomedical research. Understanding signalling processes of the immune system and how a disease or a proposed therapy modulates pathways of the immune response can provide important information for understanding disease pathology and provide new guidelines for diagnostics. Additionally, knowledge of inflammatory responses aids drug discovery and development.

Inflammatory diseases

Chronic inflammation is known to be associated with a variety of diseases including rheumatoid arthritis, inflammatory bowel disease (IBD), dermatological diseases etc. However, it is becoming increasingly clear that chronic low-level inflammation may play an important role in a wide range of other diseases. The inflammatory processes are now found to be associated to many other types of pathologies such as multiple cardiovascular and neurological diseases, diabetes and several types of cancer.

What are cytokines and chemokines?

Cytokines and chemokines are small signalling proteins secreted primarily by immune cells. Their main function is to coordinate cell growth, proliferation, and differentiation. Cytokines and their receptors participate in a diverse array of functions including innate and adaptive immunity, inflammation, immune cell differentiation, angiogenesis, tumorigenesis, development, neurobiology, and viral pathogenesis. Dysregulation of cytokine expression is a cause of immunological and inflammatory diseases, as well as other disease conditions. Many different cell types secrete chemokines, most often to attract immune cells to the site of infection or injury during innate and adaptive immune responses.

Biomarkers within oncology

Multiplex screening of 422 candidate serum biomarkers in bladder cancer patients identifies syndecan-1 and macrophage colony-stimulating factor 1 as prognostic indicators

Urothelial bladder cancer is the 9th most common type of cancer and identification of biomarkers using non-invasive methods could improve and accelerate clinical management. In the present study, Bryan et al. used PEA technology to assay disease-associated proteins in the sera of bladder cancer patients with the aim of identifying staging and prognostic biomarkers. Although none of the 422 candidate proteins showed clear discrimination of states of the disease, the multiplex screening revealed two prognostic indicators, syndecan-1 and macrophage colony stimulating factor 1 (CSF-1).

Bryan R, et al., Translational Cancer Research (2017)

Development and validation of a plasma-based melanoma biomarker suitable for clinical use

The mortality rate of melanoma has steadily increased over the last 50 years, due to diagnostic imprecision and lack of molecular biomarkers. Using the multiplexed nCounter microRNA Assay from NanoString Technologies Van Laar el at. performed whole-microRNA profiling on plasma samples from 32 patients with histologically confirmed melanoma and 16 normal controls. A classification algorithm identified 38 circulating microRNAs that had biologically and statistically significant differences between melanoma and normal plasma samples. Due to the high specificity of the nCounter technology, this algorithm has a potential to become a tool for objective diagnostic biomarker discovery for a precise and accurate detection and monitoring of melanoma.

Van Laar R, et al., British Journal of Cancer (2017)

Serum microRNAs as predictors of risk for non-muscle invasive bladder cancer

MicroRNAs (miRNAs) have been implicated in the development of nearly all cancer types and may function as promising biomarkers for early detection, diagnosis and prognosis. Using the Fluidigm Biomark HD system Lian et al. sought to investigate the role of serum miRNA as potential diagnostic biomarkers for non-muscle invasive bladder cancer (NMIBC). Eighty-nine stably detected miRNAs were tested in 10 NMIBC cases and 10 healthy controls to assess the association with NMIBC risk in both discovery and validation. Seven miRNAs were found to be significantly associated with NMIBC, suggesting that specific serum miRNA signatures may serve as non-invasive predictors of NMIBC risk.

Lian J, et al., Oncotarget (2018)

Cardiology biomarkers

Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies

Cardiovascular diseases are the largest cause of smoking-induced deaths, however there is still a lack of comprehensive analyses of protein markers in relation to smoking patterns. In this study, Huang et al. used proximity extension assay (PEA) technology to study the association between 80 circulating cardiovascular-related protein with smoking. The results from the PEA analysis showed an association between smoking and protein markers representing inflammation, endothelial dysfunction and foam cell formation, suggesting that cigarette smoking may interfere with essential parts of the atherosclerosis process.

Huang B, et al., Atherosclerosis (2016)

Notch1 is a mechano-sensor in adult arteries

In this study Mack et al. shows that the endothelial NOTCH1 receptor is responsive to shear stress, and necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation. NanoString nCounter analysis of the NOTCH1 gene expression profile in in vitro experiments revealed an increase in NOTCH1 mRNA levels following onset of laminar sheer stress. Moreover, the laminar sheer stress resulted in a positive feedback on NOTCH signalling.

Mack J, et al., Nature Communications (2017)

Neurology and neuro-inflammatory markers

Sex-specific transcriptional signatures in human depression

The incidence, symptoms and treatment of Major Depressive Disorder (MDD) points towards a major difference between the sexes, where the molecular mechanisms underlying the dimorphism remains unknown. In this article Labonté B, et al. used the nanoString nCounter technology to compare the transcription profiles of six brain regions in human and murine males and females. Their results show a large rearrangement of transcriptional patterns in MDD with very limited overlap between the two sexes, highlighting the importance of studying sex-specific treatments for MDD:

Labonté B, et al., Nature Medicine (2017)

Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

Fibromyalgia is a musculoskeletal pain condition without proper pharmacological treatment options. In this article, Bäckryd et al. used proximity extension assay (PEA) technology to study the role 92 that inflammation-related proteins plays in the pathophysiological mechanisms of fibromyalgia. A multiplex protein panel applied to cerebrospinal fluid and plasma revealed signs of both systemic inflammation and neuroinflammation in the fibromyalgia patients.

Bäckryd E, et al., Journal of Pain Research (2017)

Analysis of extracellular vesicles and exosomes

Tracing Cellular Origin of Human Exosomes Using Multiplex Proximity Extension Assays

The presence of exosomes in body fluids and their variable surface composition and content render them attractive potential biomarkers. The PEA technology is a powerful protein-screening tool that can be used to identify the parental cells of exosomes. Using multiplex PEA Larssen et al. detected protein characteristics for different cell lines and their exosomes as well as proteins common to all cell lines and exosomes. By comparing the protein profiles, it was possible to determine the cellular origin of the exosomes.

Larssen P, et al., Molecular & Cellular Proteomics (2017)

Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes

Presently circulating autoantibodies against β cell autoantigens are the only clinically available biomarkers for the diagnosis of Type 1 diabetes mellitus (T1DM). Unfortunately, these autoantibodies are not suitable for early stage disease intervention. To assess the value of exosome miRNA as biomarkers for T1DM, Garcia-Contreras et al. used NanoString nCounter technology on total RNA extracted from plasma derived exosomes. Expression analysis of 800 miRNAs revealed 7 differentially expressed candidate miRNAs with a potential use as diagnostics indicators of T1DM.

Garcia-Contreras M, et al., Scientific Reports (2017)