[General]Switching the Bait

StephenW

http://the-scientist.com/2012/02/01/switching-the-bait/
Switching the Bait -  Turning a standard technique into an unbiased screen for diagnostic biomarkers
By Edyta Zielinska |February 1, 2012               
                                                
Screening for antibody biomarkers of disease to facilitate diagnosis has been fraught with failure, despite its logical approach: stick proteins onto a microscope slide and then pour over a patient’s serum, full of disease-specific antibodies, and see what sticks. Compare the results to the serum of a healthy person, and you’ve got an antibody-protein pair that should signal disease. But of the proteins IDed employing that method, “none of them are even close” to clinical diagnosis, says Thomas Kodadek, at the Scripps Research Institute in Jupiter, Florida. Kodadek and his colleagues figured that the antibodies in the serum of an ill individual wouldn’t be likely to bind to normal biological proteins. The immune system recognizes the foreign proteins of an invading pathogen or the markers of a dying cell precisely because they are different from the body’s normal proteins. A cell involved in a disease like cancer or Alzheimer’s is more likely to produce altered proteins, either because of genetic mutations or because the disease process changes the cytoplasmic environment, causing unexpected posttranslational changes.
But trying to guess what those chemical alterations might be is difficult. “We have absolutely no freakin’ idea what those events are,” says Kodadek. So instead of coating the slide with known proteins, Kodadek coated a glass slide with a fairly random assortment of unrelated synthetic small molecules that bind serum antibodies simply because of their chemical shapes, allowing for a broad and unbiased search. “The difference is what you’re fishing with,” he says.
The method “represents a major advance in the field,” says Bill Robinson of the Stanford University School of Medicine. “It could enable the identification of the antigen targets for multiple autoimmune and other diseases.”(Cell, 144:132-42, 2011)
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STATS TALK
Comparing Methods:	THE BAIT	THE PLATFORM	COST PER SLIDE	CAPACITY OF BAIT
PROTEIN ARRAY	Unaltered protein	Glass slide with proteins	$1,500 (commercially made slides)	Several thousand per slide
KODADEK’S METHOD	Synthetic molecule	Glass slide with small molecules	$10 (lab-made slides)	Potentially millions (if beads are used in place of slides)

                                                                 

StephenW

开关诱饵

诊断标志物的偏见屏幕变成一个标准的技术

Edyta杰琳斯卡，到2012年2月1日



对疾病的抗体，以方便诊断的生物标志物的筛选一直充满失败，尽管其合乎逻辑的做法是：坚持到显微镜玻片蛋白质，然后倒在病人的血清，疾病特异性抗体，并看到什么枝。一个健康人的血清，比较的结果，并且你已经有了抗体蛋白对信号疾病。托马斯说Kodadek，斯克里普斯研究所在佛罗里达州木星，但蛋白质IDed采用这种方法，“他们都不是，甚至接近”临床诊断。 kodadek和他的同事们想出一个生病的人血清中的抗体，不会有可能绑定到正常的生物蛋白。免疫系统识别入侵的病原体或正是一个垂死的细​​胞标记的外源蛋白，因为它们是从不同的人体正常的蛋白质。在参与一种疾病，如癌症或阿尔茨海默氏症的一个细胞，是更容易产生改变的蛋白质，无论是因为基因突变，或因疾病的进程，改变了细胞质环境，造成意想不到的翻译后的变化。

但是，试图猜测这些化学变化可能是困难的。 “我们绝对没有刻着'的想法，这些事件是什么，说：”Kodadek。因此，而不是与已知的蛋白质涂层的幻灯片，Kodadek涂有相当随机的分类与合成无关，仅仅是因为它们的化学形状的血清抗体结合的小分子的玻片，从而为广泛和公正的搜索。 “不同的是，你去钓鱼，”他说。

条例草案“，斯坦福大学医学院的罗宾逊说，”法“代表了在该领域的重大进展。 “这可以使多种自身免疫性疾病和其他疾病的抗原目标的识别。”（细胞，144:132-42，2011）
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统计快讯
比较方法：饵的平台成本每张幻灯片能力诱饵
蛋白质阵列，一成不变的蛋白质与蛋白质$ 1,500（商业作出幻灯片）数千每张幻灯片载玻片
KODADEK的方法合成分子与小分子的载玻片10元（实验室制成幻灯片）可能有数百万（如果在幻灯片的地方使用珠）