Biomarker Reproducibility Challenge: A Review of Non-Nucleotide Biomarker Discovery Protocols from Body Fluids in Breast Cancer Diagnosis

Breast cancer has now become the most commonly diagnosed cancer, accounting for one in eight cancer diagnoses worldwide. Non-invasive diagnostic biomarkers and associated tests are superlative candidates to complement or improve current approaches for screening, early diagnosis, or prognosis of breast cancer. Biomarkers detected from body fluids such as blood (serum/plasma), urine, saliva, nipple aspiration fluid, and tears can detect breast cancer at its early stages in a minimally invasive way. The advancements in high-throughput molecular profiling (omics) technologies have opened an unprecedented opportunity for unbiased biomarker detection. However, the irreproducibility of biomarkers and discrepancies of reported markers have remained a major roadblock to clinical implementation, demanding the investigation of contributing factors and the development of standardised biomarker discovery pipelines. A typical biomarker discovery workflow includes pre-analytical, analytical, and post-analytical phases, from sample collection to model development. Variations introduced during these steps impact the data quality and the reproducibility of the findings. Here, we present a comprehensive review of methodological variations in biomarker discovery studies in breast cancer, with a focus on non-nucleotide biomarkers (i.e., proteins, lipids, and metabolites), highlighting the pre-analytical to post-analytical variables, which may affect the accurate identification of biomarkers from body fluids

Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract

Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study

Abstract not availableAzadeh Safarchi, Sophie Octavia, Laurence Don Wai Luu, Chin Yen Tay, Vitali Sintchenko, Nicholas Wood, Helen Marshall, Peter McIntyre, Ruiting La

Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model

Available online 2 October 2015Abstract not availableAzadeh Safarchi, Sophie Octavia, Laurence Don Wai Luu, Chin Yen Tay, Vitali Sintchenko, Nicholas Wood, Helen Marshall, Peter McIntyre, Ruiting La

Genomic dissection of Australian Bordetella pertussis isolates from the 2008-2012 epidemic

Abstract not availableAzadeh Safarchi, Sophie Octavia, Sunny Z. Wu, Sandeep Kaur, Vitali Sintchenko, Gwendolyn L. Gilbert, Nicholas Wood, Peter McIntyre, Helen Marshall, Anthony D. Keil, Ruiting La

New Pertussis Vaccines: A Need and a Challenge

Effective diphtheria, tetanus toxoids, whole-cell pertussis (wP) vaccines were used for massive immunization in the 1950s. The broad use of these vaccines significantly reduced the morbidity and mortality associated with pertussis. Because of reports on the induction of adverse reactions, less-reactogenic acellular vaccines (aP) were later developed and in many countries, especially the industrialized ones, the use of wP was changed to aP. For many years, the situation of pertussis seemed to be controlled with the use of these vaccines, however in the last decades the number of pertussis cases increased in several countries. The loss of the immunity conferred by the vaccines, which is faster in the individuals vaccinated with the acellular vaccines, and the evolution of the pathogen towards geno/phenotypes that escape more easily the immunity conferred by the vaccines were proposed as the main causes of the disease resurgence. According to their composition of few immunogens, the aP vaccines seem to be exerting a greater selection pressure on the circulating bacterial population causing the prevalence of bacterial isolates defective in the expression of vaccine antigens. Under this context, it is clear that new vaccines against pertussis should be developed. Several vaccine candidates are in preclinical development and few others have recently completed phaseI/phaseII trials. Vaccine candidate based on OMVs is a promising candidate since appeared overcoming the major weaknesses of current aP-vaccines. The most advanced development is the live attenuated-vaccine BPZE1 which has successfully completed a first-in-man clinical trial.Fil: Hozbor, Daniela Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentin