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人类细胞组计划的潜力与挑战。

Potential and challenges of a human cytome project.

作者信息

Valet G, Tárnok A

机构信息

Max-Planck-Institut für Biochemie, Martinsried, Germany.

出版信息

J Biol Regul Homeost Agents. 2004 Apr-Jun;18(2):87-91.

Abstract

BACKGROUND

The elucidation of the molecular pathways from the 20-40.000 genes of the sequenced human genome via investigation of genetic networks and molecular pathways up to the cellular and organismal phenotypes is highly complex and time consuming.

STRATEGY AND GOALS

The proposed upside-down research strategy of a human cytome project accesses the expressed molecular cell phenotypes by differential screening, for example of diseased versus healthy, or undifferentiated versus differentiated cells to obtain information on disease or differentiation related molecular hotspots at the single cell level. The genome serves as inventory of the biomolecular capacities of organisms while the mechanisms of genome realisation are initially entirely bypassed. Detected molecular hotspots are further investigated by backward directed systems biology, including molecular pathway modelling to elucidate disease related molecular pathways. New drug targets may be identified to specifically influence such pathways. Differential screening provides, in addition, individualized disease course predictions for everyday medicine, in form of "predictive medicine by cytomics." The early recognition of future disease complications enables an immediate application of preventive therapies. This is likely to lower disease related irreversible tissue destruction and adverse drug reactions and will allow to individually optimize patient therapy.

OUTLOOK

Immediate medical use, facilitated access to the detection of new drug targets, increased research speed and the stimulation for advanced technological developments represent major driving forces for the efforts to establish a human cytome project.

摘要

背景

从已测序人类基因组的20000至40000个基因出发,通过研究遗传网络和分子途径直至细胞及机体表型,来阐明分子途径极为复杂且耗时。

策略与目标

拟议的人类细胞组计划的颠倒式研究策略,通过差异筛选来获取表达的分子细胞表型,例如对患病细胞与健康细胞、未分化细胞与分化细胞进行差异筛选,以在单细胞水平上获取与疾病或分化相关的分子热点信息。基因组作为生物体生物分子能力的清单,而基因组实现机制最初则完全被绕过。通过反向系统生物学进一步研究检测到的分子热点,包括分子途径建模以阐明与疾病相关的分子途径。可能会确定新的药物靶点以特异性影响此类途径。此外,差异筛选以“细胞组学预测医学”的形式为日常医学提供个性化的疾病进程预测。对未来疾病并发症的早期识别能够立即应用预防性治疗。这可能会减少与疾病相关的不可逆组织损伤和药物不良反应,并允许对患者治疗进行个体化优化。

展望

直接的医学应用、便于发现新的药物靶点、提高研究速度以及刺激先进技术发展,是推动建立人类细胞组计划各项努力的主要动力。

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