模型预测造成出生缺陷的药物的可能性

生物信息学在药物作用的基因在胎儿发展分析处理数据

2011年1月4日
波士顿，大众。——当孕妇需要药物治疗时，经常会关注胎儿可能产生的影响。虽然有些药物被清楚地认识到导致出生缺陷（反应停是一个臭名昭著的例子），和其他人通常被认为是安全的，令人惊讶的是鲜为人知的是，大多数药物的风险水平。波士顿儿童医院的研究人员信息计划（芯片）对预测药物的致畸性创造了一个临床前模型（导致胎儿畸形倾向）基于特征的基因，它的目标。

该模型，在3月2011日的问题生殖毒理学（出版在线in November), used bioinformatics and public databases to profile 619 drugs already assigned to a pregnancy risk class，和 whose target genes or proteins are known。 For each of the genes targeted, 7426 in all, 芯片 investigators亚瑟Schachter，MD，MMSC，MS，和艾萨克小羽，医学博士，哲学博士分析数据库，以确定参与胎儿发育相关的生物学过程的基因，寻找这样的搜索词如“成因”的发展，“分化”或“增长”。

研究人员发现，药物靶向与胎儿发育相关的基因比例很大，这些基因往往是高风险类的。基于发展的基因图谱，他们创建了一个模型，显示百分之79的准确预测药物是否会在课堂上（安全）或X类（已知的致畸剂）。

例如，降胆固醇药物西立伐他汀、洛伐他汀、普伐他汀、氟伐他汀均在X类，所有这些药物也有很高比例的高风险基因（98到百分之100）。抗凝血药的抗凝血药，也在第十类，有一个比例为百分之88。

当Schachter和小羽的模型应用在所有风险类药物，发育基因的比例目标大致匹配已知的风险程度（见图表）。然而，该模型在Schachter愿意分享特殊药品的实际预测还需要进一步的验证。”“我们不希望有必要的药物，”他说：“怀孕妇女的风险。

这个图是五个目前公认的怀孕风险类别（一个，乙，丙，丁和×），显示出越来越多的比例的类药物，丙和丁针对一个或多个“高风险”的基因（有针对性的类药物，但从来没有类药物）。

One difficulty in validating the model is that the "known" teratogenicity it's being tested against often isn't known。 Between Class A and Class X are Classes B, C and D, with increasing amounts of risk, but the boundaries between them are based on minimal data。 Teratogenic effects may be difficult to spot, since most drugs are taken relatively rarely in pregnancy, some may be taken along with other drugs，和 any effects tend to be rare or too subtle to be noted in medical records。 Moreover, data from animal testing doesn't necessarily apply to humans。

"A lot of drugs in the middle of the spectrum，和 maybe even some in Class A, may cause subtle defects that we haven't detected," says Schachter。 "We can't provide a yes/no answer, but we found a pattern that can predict which are riskier。"

Given the degree of uncertainty, Schachter and Kohane believe their model may be of interest to drug developers and prescribing physicians，和 might provide useful information to incorporate in drug labeling。

“现在我们可以对病人说，“这种药物靶点一吨的基因在发育过程中，'说：”节目。

或者，相反，如果一个年轻的孕妇有一个心脏病，需要治疗，医生可以放心，心脏药物的配置文件，他补充说。“我们不知道，”我们现在可以说，这种药物在怀孕期间更安全。”

"We have here a prismatic example of the utility of a big-picture, macrobiological approach," says Kohane, director of 芯片。 "By combining a comprehensive database of protein targets of drugs and a database of birth defects associated with drugs, we find a promising predictive model of drug risk for birth defects。"

这项研究是由一项拨款资助的国家普通医学科学研究所。

接触：
克里斯特德曼
617-919-3110
keri。stedman@childrens。harvard。edu

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869。 More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community。 Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 392-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families。 Children's also is the primary pediatric teaching affiliate of Harvard Medical School。 For more information about research and clinical innovation at Boston Children's visit:向量博客。

（注：转载时请注明复诊网）