Liquid biopsies for monitoring the health status of blue mussels

由于其在组织中积累外来物质的能力，广泛的分布，以及生态和经济的重要性，蓝色贻贝长期以来被认为是监测污染和气候变化对海洋生态系统影响的良好生物指标。因此，已经开发了相对大量的生物标志物来确定蓝色贻贝的健康状况。这些生物标志物可以及早检测到因暴露于应激源而导致的生物学变化，这可能会导致长期的生理障碍。在最常见的生物标记物中，有反映形态变化的组织学生物标记物和反映基本细胞机制变化的功能生物标记物。然而，在大多数情况下，这些方法需要经过现场训练的组织解剖和/或不间断的冷链采样，以保持样本的质量。对于偏远地区，如极地地区的抽样，这意味着复杂的后勤挑战以及与运输和储存相关的相当大的风险和成本。这些困难是长期监测气候变化对海洋生态系统影响的主要障碍。支撑组学技术的高通量过程的出现为克服这些障碍和开发与现代采样技术兼容的“下一代生物标记物”提供了新的机会。在医学上，这些生物标记物已经导致癌症和其他疾病的临床管理发生了重大转变。在这里，我们建议利用这一领域已经取得的巨大进展，特别关注液体活检的概念。通过使用少量血液样本，临床医生可以轻松、快速地获得重要信息，这些信息用于评估正在进行的组织损伤或高精度地衡量特定治疗的疗效。我们建议应用这一概念，并将其与Flinders Technology Associates(FTA)卡相结合，以开发基于组学的新型生物标记物。我们将使用这种方法来研究不同栖息地类型的贻贝在不同的时空条件下的细菌微生物群。我们还将表征和研究贻贝血浆中循环中的无细胞DNA(CcfDNA)片段，特别是循环中的病毒体和甲基组。最后，我们将进行实验室实验，研究胁迫因素对贻贝ccfDNA和细菌微生物群的影响。在短期内，这些研究将有助于更好地了解贻贝与其环境之间的关系。这也将促进我们对贻贝暴露于人类活动后与压力相关反应的发展所涉及的病理生理机制的了解。从长远来看，该计划将有助于开发下一代基于多组学的生物标记物，用于纵向监测海洋生态系统健康。

Because of their ability to accumulate xenobiotics in their tissues, wide distribution, and ecological and economical importance, blue mussels have long been recognized as good biological indicators for monitoring the effects of pollution and climate change in marine ecosystems. A relatively large number of biomarkers have thus been developed to determine the health status of blue mussels. These biomarkers allow early detection of biological changes due to exposure to stressors, which may result in long-term physiological disturbances. Among the most common biomarkers, there are histological biomarkers, which reflect morphological alterations, and functional biomarkers, which reflect alteration in basic cellular mechanisms. In most cases, however, these approaches require on-site trained tissue dissection and/or uninterrupted cold chain sampling to maintain quality of samples. For sampling in remote areas, such as polar regions, this implies complex logistical challenges and considerable risk and cost associated with shipment and storage. These difficulties represent a major obstacle for long-term monitoring of impacts of climate change in marine ecosystems. The advent of high-throughput processes underpinning omics technologies provides a new opportunity to overcome these obstacles and to develop “next-generation biomarkers” that are compatible with modern sampling technologies. In medicine, these biomarkers have led to a significant shift in the clinical management of cancer and other diseases. Here, we propose to take advantage of the tremendous progress that has been achieved in this field with a particular attention to the concept of liquid biopsy. Using a small sample of blood, clinicians can easily and quickly obtain vital information that are used to assess ongoing tissue damage or to measure with high precision the efficacy of a given treatment. We propose to apply this concept and combine it with the Flinders Technology Associates (FTA) cards for the development of novel omics-based biomarkers. We will use this approach to study the bacterial microbiome of mussels in different habitat types across temporally and spatially varying conditions. We will also characterize and study circulating cell-free DNA (ccfDNA) fragments in plasma of mussels, with a particular attention to the circulating virome and methylome. Finally, we will conduct laboratory experiments to study the effects of stress factors on ccfDNA and the bacterial microbiome of mussels. On a short-term basis, these studies will contribute to a better understanding of the relationship between mussels and their environment. It will also allow advance our knowledge on the pathophysiologic mechanisms implicated in the development of stress-related responses of mussels following exposure to anthropogenic activities. On a long-term basis, the program will help to develop next-generation multi-omics-based biomarkers for longitudinal monitoring of marine ecosystem health.*****************