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注:WCG官网已有中文版本
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非专业人士业余瞎翻译,如有谬误,欢迎指正
项目FAQ(已翻译)
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Help Conquer Cancer
帮助征服癌症
Project Status and Findings:
项目状况与结果:
Information about this project is provided on the web pages below and by the project scientists on the Help Conquer Cancer website. To comment or ask questions about this project, please submit a post in the Help Conquer Cancer forum.
有关本项目的信息在网页下方;在“帮助征服癌症”网页也有项目科学家提供的信息。如需对项目发表评论或提出问题,请至“帮助征服癌症”论坛发帖。
Mission
任务
The mission of Help Conquer Cancer is to improve the results of protein X-ray crystallography, which helps researchers not only annotate unknown parts of the human proteome, but importantly improves their understanding of cancer initiation, progression and treatment.
“帮助征服癌症”项目的任务是改善蛋白质X射线结晶学的效果。这不仅能帮助研究人员注解人类蛋白的未知部分,更重要的是帮助他们提升对癌症的产生、发展及治疗的了解。
Significance
意义
In order to significantly impact the understanding of cancer and its treatment, novel therapeutic approaches capable of targeting metastatic disease (or cancers spreading to other parts of the body) must not only be discovered, but also diagnostic markers (or indicators of the disease), which can detect early stage disease, must be identified.
为了更有效的影响对癌症及其治疗的理解,不仅需要找出提议以新陈代谢疾病(或在人体内蔓延的癌症)为目标的新型疗法,而且必须能够查出查出早期疾病的症状标记(或疾病指示)。
Researchers have been able to make important discoveries when studying multiple human cancers, even when they have limited or no information at all about the involved proteins. However, to better understand and treat cancer, it is important for scientists to discover novel proteins involved in cancer, and their structure and function.
研究人员已在对多种人类癌症的研究中得到了很多重大发现,甚至在他们仅有部分或根本没有相关蛋白质的信息的情形之下。然而为了更好的了解和治疗癌症,科学家们发现与癌症相关的新型蛋白质及其结构和功能就显得十分重要。
Scientists are especially interested in proteins that may have a functional relationship with cancer. These are proteins that are either over-expressed or repressed in cancers, or proteins that have been modified or mutated in ways that result in structural changes to them.
科学家对可能与癌症有功能关系的蛋白质特别有兴趣。这包括在癌症中被过表达(?)或被抑制的蛋白质,以及那些被修改或被转变并从而导致结构性变化的蛋白质。
Improving X-ray crystallography will enable researchers to determine the structure of many cancer-related proteins faster. This will lead to improving our understanding of the function of these proteins and enable potential pharmaceutical interventions to treat this deadly disease.
改进的X射线结晶学将使研究人员更快地测定多种与癌症相关的蛋白质的结构。这将提高我们对这些蛋白质功能的了解,并有助于发现可能治愈这些致死疾病的药物。
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About the Project
关于“帮助征服癌症”项目
X-ray Crystallography
X射线结晶学
One of the favored methods for protein-structure determination is X-ray crystallography. Through this method, scientists use the high-throughput crystallization pipeline to help annotate unknown parts of the human proteome, which in turn will help to improve their understanding of cancer initiation, progression and treatment.*
X射线结晶学是一种极受欢迎的蛋白质机构测定方法。通过这种方法,科学家使用高吞吐量(?)结晶化管道来帮助注解(?)人类蛋白的未知部分。反过来这也会有助于提高科学家对癌症产生、发展及治疗的了解。(*参1#末尾处)
There are two main steps involved in X-ray crystallography:
X射线结晶学有两个主要步骤:
1. Crystallizing the protein: Although a lot more complex, this is similar to putting sugar into a cup of water and letting it sit for a while. Once the water evaporates, tiny sugar crystals appear.
1. 使蛋白质结晶:这就好比把糖置入一杯水中并保持一段时间一样,当水蒸发之后,微小的糖晶体就会显现出来。当然,蛋白质结晶的过程要比这复杂的多。
2. Sending X-rays through the crystal: Depending on how they diffract, a mathematical model is used to determine and observe the protein's structure.
2. 令X射线穿过晶体:我们使用一个数学模型根据通过它们时产生的衍射来测量和观察蛋白质结构。
Crystallizing the protein is not a straightforward procedure. There are many thousands of possible conditions that affect the process (concentration of a protein and solution, temperature, pH, chemical additives, etc.), but scientists must find the appropriate combination of these conditions for a protein to crystallize. For example, with sugar, if you change the water to another liquid, change the temperature or concentrations, you may not get a crystal. Similarly, for a given protein, the challenge is to know what conditions will lead to forming a crystal — what solution, what temperature, pH, etc.
将蛋白质结晶化并非是一个简单的过程。有数千种情形(蛋白质溶液的浓度、温度、酸碱度、化学附加物,等等)都可能会影响这一过程。但科学家必须找到能够适合蛋白质结晶的上述各个条件。拿糖来说,如果您把水换成其他液体,改变温度或浓度,就有可能无法得到结晶。同样的,对于给定的蛋白质来说,挑战就在于如何知道什么样的条件才能形成晶体——何种溶液、何种温度、酸碱度,等等。
The resultant protein crystal also must be well-formed and large enough in order for x-rays to detect the protein's structure at high resolution. If the conditions are not perfect for crystallizing the protein, the process can result in either a micro-crystal, which is too small for the protein's structure to be determined; a precipitate, which shows some changes, but does not lead to crystallization event directly; or no change may have occurred at all.
为了用X射线侦测高解析度的蛋白质结构,我们需要合成出成型良好并且足够大的的蛋白质晶体。如果结晶化蛋白质的条件无法很好的满足,这一过程就可能得到一个由于过小而导致无法测定蛋白质结构的微晶体;或是能够显示某些变化,但却无法直接完成结晶化过程;或者根本不起任何变化。
Frustrating the situation is that, as yet another barrier to progress, usually the more important the protein is to cancer research, the harder that protein is to crystallize. Many proteins involved in cancer are long chains, or they require additional proteins to properly fold and cannot be crystallized by themselves.
令人沮丧的是,至今为止另一个阻碍我们前进的是,通常对于癌症研究越重要的蛋白质就越难以被结晶化。许多与癌症相关的蛋白质都是长链,或者它们需要额外的蛋白质才能正确的折叠,并且无法单独结晶化它们。
In order to run the millions of combinations necessary to successfully crystallize a protein, scientists have used robots to perform the work. Robots are able to put in place the various crystallization conditions faster and more accurately. To further facilitate the process, result of each of the millions of crystallization experiments are photographed.
为了进行成功结晶化蛋白质所必需的数百万次合成试验,科学家使用了机器人来完成这项工作。机器人能够更快更准确的完成不同结晶化条件的试验工作。为了更加促进这一进程,这全部的数百万次结晶化试验都被用照片记录了下来。
Currently, scientists at the Hauptman-Woodward Medical Research Institute (HWI) in Buffalo have run more than 86 million crystallography experiments for more than 9,400 proteins. As a result, they have 86 million pictures of these proteins that have gone through the X-ray crystallography high-throughput screening pipeline. Each of these pictures needs to be analyzed to determine what the result of the experiment is — i.e., crystal, precipitate, phase separation, skin effect, no change.
现在,位于布法罗的豪普特曼-伍德沃德医学研究院(HWI)的科学家们已经对9400多种蛋白质进行了超过8600万次的结晶学试验。作为结果,他们通过X射线结晶学高吞吐量(?)拍摄管道得到了这些蛋白质的8600万张照片。每张照片都需要被分析测定试验的结果如何——即,结晶,沉淀,相位分离,表面效应,无改变。(?)
One of the challenges is the tremendous size of these datasets, which requires over 25 TB of storage (or equivalent to more than 9,000 DVDs). IBM's Blue Gene supercomputer has provided assistance in this phase of the work, by running a special image compression algorithm to reduce the size of these images without losing content. The other challenge is to comprehensively analyze an image to determine the crystallization outcome, a task that requires approximately 10 hours to process on a single computer. Researchers would thus require almost 100,000 years to analyze the existing pictures.
有一个挑战就是这些数据实在太多了。它们总计超过了25TB(相当于9000多张DVD)。IBM的蓝色基因超级计算机为我们这一阶段的工作提供了帮助。它通过一个专门的图像压缩计算法则来对这些图像进行无损压缩(译注:BiscuiT似乎比较喜欢无损)。还有个挑战是,需要在一台通用计算机上运算大约10个小时才能够全面分析一张图像并测定结晶化的结果。这样一来,研究人员将需要几乎100,000年来分析现有的这些照片。
World Community Grid and "Help Conquer Cancer"
WCG与“帮助征服癌症”
Using the power of World Community Grid, scientists at the Ontario Cancer Institute (OCI), Princess Margaret Hospital, and the University Health Network will process the existing 86 million images of proteins that have been screened in the high-throughput crystallization pipeline at HWI. World Community Grid will run a CrystalVision program that the researchers at OCI have developed to analyze the features of individual images to determine the outcome of the crystallization screen — crystal, micro crystal, phase separation, skin, precipitate, or no change.
通过借助WCG的力量,安大略癌症研究院(OCI)、玛格丽特公主医院以及健康网络大学的科学家得以对HWI的高吞吐量结晶化管道所拍摄的8600万张蛋白质图像进行处理。WCG通过OCI的研究人员开发的CrystalVision程序来分析每幅图片的特征,测定结晶化拍摄的结果——晶体,微晶体,相位分离,表面效应,沉淀,或是无改变。(?)
If a crystal occurs, crystallographers can put the protein through the optimization process to determine the optimal conditions for the crystallization, and in turn perform a diffraction experiment to determine the structure of the protein. What's more, scientists can compare proteins that have successfully crystallized against proteins of unknown structure that have similar characteristics, based on the results from the crystallization screen. This can be the starting point for crystallization for these proteins so that their structure can be determined.
如果发生了结晶,检测仪就会让该蛋白质进行这个最优化的过程,以此来检测这一结晶化的最优化条件,并进行衍射试验来测定蛋白质的结构。此外,科学家还将在基于结晶化拍摄结果的基础上,把成功结晶的蛋白质与具有相似特性但不知结构的蛋白质进行对比。这会是对这些蛋白质结晶化的出发点,并因此能够测定它们的结构。
If the crystal produced was not well-formed or large enough, scientists can still use the information to help them better determine the conditions necessary to create a well-formed crystal. For example, they may learn that Protein X and Condition A resulted in a micro crystal, and Protein A and Condition Z resulted in a micro crystal as well. Based on this information, they can then run additional experiments to deduce what conditions need to be optimized to create a larger and more well-formed crystal.
如果没能得到成型良好或足够大的晶体,科学家仍可利用这些信息来帮助他们更好的测定得到成型良好的晶体的必需条件。举例来说,他们发现蛋白质X和条件A导致了微晶体,蛋白质A和条件Z也导致了微晶体。基于这些信息,他们能够进行附加试验来推论需要优化何种条件以便于制出更大、成型更好的晶体。
Analyzing the results from this experiment will also lead to better understanding the underlying principles of protein crystallography. For the first time, a comprehensive crystallography image analysis will be done, which was impossible before due to computational complexity. In turn, CrystalVision will be improved to provide faster and more accurate image classification.
分析这一试验的结果还能够更好的了解蛋白质结晶学的根本原理。一个全面的结晶学图像分析将首次被完成,而这在以前由于计算的复杂性是不可能完成的。反过来,CrystalVision将会被改进,以便于提供更快更准确的图像分类。
Improving the protein crystallography pipeline will enable researchers to determine the structure of many cancer-related proteins faster. This will lead to improving our understanding of the function of these proteins, and enable potential pharmaceutical interventions to treat this deadly disease.
改进的蛋白质结晶学管道将使研究人员更快地测定多种与癌症相关的蛋白质的结构。这将提高我们对这些蛋白质功能的了解,并有助于发现可能治愈这些致死疾病的药物。
* There are other approaches to understanding the structure and function of proteins, including the method used in the Human Proteome Folding Project also running on World Community Grid. Given the essential nature of this work, it's important to advance every research technique to complete our understanding of the human organism and disease.
* 其他一些方法也可以了解蛋白质的结构和功能,包括同样运行于WCG的人类蛋白质折叠项目所采用的方法。基于这项工作的本质,最重要的就是提升每项研究技术来完成我们对人类组织和疾病的认识。
[ 本帖最后由 Julian_Yuen 于 2009-1-30 19:16 编辑 ] |
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