Molecular Methods for Detection of Antimicrobial Resistance

ABSTRACT The increase in bacteria harboring antimicrobial resistance (AMR) is a global problem because there is a paucity of antibiotics available to treat multidrug-resistant bacterial infections in humans and animals. Detection of AMR present in bacteria that may pose a threat to veterinary and public health is routinely performed using standardized phenotypic methods. Molecular methods are often used in addition to phenotypic methods but are set to replace them in many laboratories due to the greater speed and accuracy they provide in detecting the underlying genetic mechanism(s) for AMR. In this article we describe some of the common molecular methods currently used for detection of AMR genes. These include PCR, DNA microarray, whole-genome sequencing and metagenomics, and matrix-assisted laser desorption ionization–time of flight mass spectrometry. The strengths and weaknesses of these methods are discussed, especially in the context of implementing them for routine surveillance activities on a global scale for mitigating the risk posed by AMR worldwide. Based on current popularity and ease of use, PCR and single-isolate whole-genome sequencing seem irreplaceable.</jats:p

Guidelines for investigating causality of sequence variants in human disease

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development

Integrating precision cancer medicine into healthcare—policy, practice, and research challenges

Abstract Precision medicine (PM) can be defined as a predictive, preventive, personalized, and participatory healthcare service delivery model. Recent developments in molecular biology and information technology make PM a reality today through the use of massive amounts of genetic, ‘omics’, clinical, environmental, and lifestyle data. With cancer being one of the most prominent public health threats in developed countries, both the research community and governments have been investing significant time, money, and efforts in precision cancer medicine (PCM). Although PCM research is extremely promising, a number of hurdles still remain on the road to an optimal integration of standardized and evidence-based use of PCM in healthcare systems. Indeed, PCM raises a number of technical, organizational, ethical, legal, social, and economic challenges that have to be taken into account in the development of an appropriate health policy framework. Here, we highlight some of the more salient issues regarding the standards needed for integration of PCM into healthcare systems, and we identify fields where more research is needed before policy can be implemented. Key challenges include, but are not limited to, the creation of new standards for the collection, analysis, and sharing of samples and data from cancer patients, and the creation of new clinical trial designs with renewed endpoints. We believe that these issues need to be addressed as a matter of priority by public health policymakers in the coming years for a better integration of PCM into healthcare