探究疾病的深处

简介: Advancing our understanding of disease biology is the only way we will uncover novel drivers for those diseases we aim to treat, 希望预防和将来, 甚至治愈. The advent of multi-omics is allowing scientists to probe the more complex and transient molecular changes that underpin the course of disease and response to treatment, 帮助澳门第一赌城在线娱乐更好地选择正确的药物靶点.

揭示基因组之外的秘密

Genomics – the mapping of all human genes and their interactions with each other – has been a game-changer in drug discovery and clinical research, 支撑着向精准医疗的转型. 但在基因组之外，还有转录组的动态领域, proteome and metabolome – largely untapped repositories of rich information that if connected could tell us more about what is driving disease. 多组学是这些数据集的集成, 通过技术的进步, 现在开始揭示新的见解了吗.

揭示有希望的新药物靶点, it is vital to get a true understanding of the downstream ‘omes’ programmed by the genome, 即转录组(RNA读出的总数), proteome (the totality of protein produced) and metabolome (the totality of the metabolites that result). While genomics provides a static view - the DNA ‘blueprint’ - the other ‘omes’ are dynamic and subject to change under different conditions. 转录组的, 例如, can reveal the extent to which each gene is turned on or off within cells, 类似于调光开关.

通过生物信息学和人工智能, we can use this omic data to create multi-dimensional models of the whole hierarchical system in healthy, 患病和治疗状态. This has far-reaching implications for drug discovery giving us the potential to spot potential new drug targets and validate them. 澳门第一赌城在线娱乐可以预测毒性. We can also develop biomarkers for downstream accompanying diagnostics in the field. 最终, multi-omics is an enabler for predictive science across our whole organisation: with the help of machine learning and AI, we can use it to predict what a drug molecule does in a cell with far greater certainty.

多组学的目标很简单

这些技术把科学家变成了分子侦探

在转录组, we employ the most advanced technologies available with the aim of generating smart, 动态和无偏的数据. As well as single-cell sequencing (a technique that sequences individual cells’ RNA within the context of their micro-environments), 这些包括:

• A state-of-the-art next generation sequencer which generates 10 billion sequences in one run (the equivalent to 23 whole genomes in two days)
• Spatial transcriptomics which allows us to analyse the transcriptome within intact tissue sections, preserving cells in their morphological context to better understand function
• Portable nanopore technology which uses biophysics to pull RNA molecules through fine holes in a membrane, 实时创建可读的电气变化. This allows for long range (whole molecule) sequencing on the move – all in a matter of seconds, enabling the accurate identification of complex alternative splice variants

在蛋白质组学和代谢组学中, we use state-of-the-art mass spectrometry to identify and quantify proteins, metabolites and lipids and work out which changes occur during disease or after treatment. 这项技术非常精确, 有足够的分辨率, we can differentiate between an oxidised protein and a citrullinated protein.

Our mass spectrometry instruments can identify five thousand protein molecules in less than an hour. We can probe even deeper within the proteome into the so-called ‘fourth dimension’ of ion mobility using a technique called timsTOF – and thereby determine ever more subtle proteomic characteristics.

Advancing technology making the impossible possible and the possible easier

Multi-omics instrumentation is advancing every one to two years and each time we achieve 25% more than we could before, 就像放大谷歌地图一样. 不仅仅是灵敏度和分辨率在提高. Speed, throughput and specificity are too – and less and less material is needed for each analysis. 它让不可能成为可能，让可能变得更容易. 以技术创新为动力, multi-omics is proving to be one of the richest sources of data in all of discovery science.