The impact of comparative genomics on infectious disease research

The past decade has witnessed a revolution in infectious disease research, fuelled by the accumulation of a huge amount of DNA sequence data. The avalanche of genome sequence information has largely promoted the development of comparative genomics, which exploits available genome sequences to perform either inter- or intra-species comparisons of bacterial genome contents, or performs comparisons between the human genome and those of other organisms. This review aims to summarize how comparative genomics is being extensively used in infectious disease research, such as in the studies to identify virulence determinants, antimicrobial drug targets, vaccine candidates and new markers for diagnostics. These applications hold considerable promise for alleviating the burden of infectious diseases in the coming years.     

The impact of genomics on discovering drugs against infectious diseases

Genomics is accelerating the progress in data generation and interpretation in the global analyses of components of cells, including the spectrum of lipids, RNA, metabolites, proteins, mutational phenotypes or DNA methylation sites. Integration of the knowledge generated by these diverse strategies is predicted to have a tremendous impact on approaches to rational drug discovery against infectious diseases.     

The impact zone: genomics and breeding for durable disease resistance

Durable disease resistance is a major but elusive goal of many crop improvement programs. Genomic approaches will have a significant impact on efforts to ameliorate plant diseases by increasing the definition of and access to genepools available for crop improvement. This approach will involve the detailed characterization of the many genes that confer resistance, as well as technologies for the precise manipulation and deployment of resistance genes. Genomic studies on pathogens are providing an understanding of the molecular basis of specificity and the opportunity to select targets for more durable resistance. There are, however, several biological and societal issues that will have to be resolved before the full impact of genomics on breeding for disease resistance is realized.     

The importance of who infects whom: the evolution of diversity in host resistance to infectious disease

Variation for resistance to infectious disease is ubiquitous and critical to host and parasite evolution and to disease impact, spread and control. However, the processes that generate and maintain this diversity are not understood. We examine how ecological feedbacks generate diversity in host defence focussing on when polymorphism can evolve without co-evolution of the parasite. Our key result is that when there is heritable variation in hosts in both their transmissibility and susceptibility along with costs to resistance, there is the possibility of the evolution of polymorphism. We argue that a wide range of behavioural or physiological mechanisms may lead to relationships between transmissibility and susceptibility that generate diversity. We illustrate this by showing that a tendency for higher contacts between related individuals leads to polymorphism. Only dimorphisms can evolve when infection is determined only by an individuals' susceptibility or when transmissibility and susceptibility are simply positively or negatively correlated.     

Empowering African genomics for infectious disease control

At present, African scientists can only participate minimally in the genomics revolution that is transforming the understanding, surveillance and clinical treatment of infectious diseases. We discuss new initiatives to equip African scientists with knowledge of cutting-edge genomics tools, and build a sustainable critical mass of well-trained African infectious diseases genomics scientists.     

Bacterial population genomics and infectious disease diagnostics

New sequencing technologies have made the production of bacterial genome sequences increasingly easy, and it can be confidently forecasted that vast genomic databases will be generated in the next few years. Here, we detail how collections of bacterial genomes from a particular species (population genomics libraries) have already been used to improve the design of several diagnostic assays for bacterial pathogens. Genome sequencing itself is also becoming more commonly used for epidemiological, forensic and clinical investigations. There is an opportunity for the further development of bioinformatic tools to bring even further value to bacterial diagnostic genomics.     

The thermal mismatch hypothesis explains host susceptibility to an emerging infectious disease

Parasites typically have broader thermal limits than hosts, so large performance gaps between pathogens and their cold‐ and warm‐adapted hosts should occur at relatively warm and cold temperatures, respectively. We tested this thermal mismatch hypothesis by quantifying the temperature‐dependent susceptibility of cold‐ and warm‐adapted amphibian species to the fungal pathogen Batrachochytrium dendrobatidis (Bd) using laboratory experiments and field prevalence estimates from 15 410 individuals in 598 populations. In both the laboratory and field, we found that the greatest susceptibility of cold‐ and warm‐adapted hosts occurred at relatively warm and cool temperatures, respectively, providing support for the thermal mismatch hypothesis. Our results suggest that as climate change shifts hosts away from their optimal temperatures, the probability of increased host susceptibility to infectious disease might increase, but the effect will depend on the host species and the direction of the climate shift. Our findings help explain the tremendous variation in species responses to Bd across climates and spatial, temporal and species‐level variation in disease outbreaks associated with extreme weather events that are becoming more common with climate change.     

Genetics and genomics in infectious disease susceptibility.

The past decade has witnessed a rapid transition from the first positional cloning of an infectious disease susceptibility gene (Slc11a1, also called Nramp1) in the mouse to genome-wide scans in human multicase families and the identification of potential disease-causing genes by simple inspection of the public human genome databases. Pathogen genome projects have facilitated multilocus sequence typing of pathogen isolates and studies of ecological fitness and virulence patterns in disease-causing isolates. Comparative sequence analysis of pathogen strains and functional genomics studies are now underway, hopefully providing new insight into infectious disease susceptibility.     

儿童感染性眼病的病原菌分布特征及耐药性分析

目的探讨儿童感染性眼病的感染病原菌菌群分布及药敏分析。方法回顾性分析2010年12月至2014年2月我院眼科门诊及住院部的526例感染性眼病的患儿的临床资料。结果送检病原体标本的培养阳性数共为157例,培养阳性率为29.8%。其中细菌标本134例(占85.3%),真菌标本21例(占13.4%),阿米巴2例(占1.3%)。阳性标本的年龄分布≤l岁的标本数最多且全部为细菌感染;共培养鉴定出细菌206株,其中革兰阳性球菌占45.6%,革兰阴性杆菌占15.5%。培养的细菌中,淋球菌比例最高,占18.4%,且均来自1岁以下幼儿。1岁以上幼儿最常见为表皮葡萄球菌(17.9%)。培养阳性细菌中,左氧氟沙星及利福平的药物敏感性显著高于其他药物;培养阳性的真菌中,对那他霉素敏感性最高。结论儿童感染性眼病致病因素和病原菌的分布与成人相比,均有所不同,所以眼科医师要更深入全面了解其病原菌的分布和敏感性药物的特点。     

The impact of next-generation sequencing on genomics

This article reviews basic concepts,general applications,and the potential impact of next-generation sequencing(NGS)technologies on genomics,with particular reference to currently available and possible future platforms and bioinformatics.NGS technologies have demonstrated the capacity to sequence DNA at unprecedented speed,thereby enabling previously unimaginable scientific achievements and novel biological applications.But,the massive data produced by NGS also presents a significant challenge for data storage,analyses,and management solutions.Advanced bioinformatic tools are essential for the successful application of NGS technology.As evidenced throughout this review,NGS technologies will have a striking impact on genomic research and the entire biological field.With its ability to tackle the unsolved challenges unconquered by previous genomic technologies,NGS is likely to unravel the complexity of the human genome in terms of genetic variations,some of which may be confined to susceptible loci for some common human conditions.The impact of NGS technologies on genomics will be far reaching and likely change the field for years to come.     

The impact of genomics on mammalian neurobiology

The benefit of genomics lies in the speeding up of research efforts in other fields of biology, including neurobiology. Through accelerated progress in positional cloning and genetic mapping, genomics has forced us to confront at a much faster pace the difficult problem of defining gene function. Elucidation of the function of identified disease genes and other genes expressed in the Central nervous system has to await conceptual developments in other fields.     

The impact of bacteriophage genomics

The discovery of (bacterio)phages revolutionised microbiology and genetics, while phage research has been integral to answering some of the most fundamental biological questions of the twentieth century. The susceptibility of bacteria to bacteriophage attack can be undesirable in some cases, especially in the dairy industry, but can be desirable in others, for example, the use of bacteriophage therapy to eliminate pathogenic bacteria. The relative ease with which entire bacteriophage genome sequences can now be elucidated has had a profound impact on the study of these bacterial parasites.