Genome Medicine:中科院北京生科院赵方庆团队发表识别非编码区致病性变异的新成果

2018-07-12 佚名 中国生物技术网

国际学术期刊Genome Medicine发表了中国科学院北京生命科学研究院赵方庆团队题为“Prioritization and functional assessment of noncoding variantsassociated with complex diseases”的最新研究成果。如何解读与复杂疾病有关的遗传变异,尤其是非编码区变异,是疾病遗传学领域的一个巨大挑战。现有方法在评估非

国际学术期刊Genome Medicine发表了中国科学院北京生命科学研究院赵方庆团队题为“Prioritization and functional assessment of noncoding variantsassociated with complex diseases”的最新研究成果。如何解读与复杂疾病有关的遗传变异,尤其是非编码区变异,是疾病遗传学领域的一个巨大挑战。现有方法在评估非编码区致病性变异方面存在着假阳性率过高、敏感度不够等问题。该研究首次提出一种全新的基于人群等位基因频率谱的监督集成算法(PAFA),实现对复杂疾病和性状相关的遗传变异进行打分识别及功能性评估。

为了解决现有方法在识别非编码区功能性变异方面面临的灵敏度低、可靠性差的问题,PAFA算法引入了丰富的知识库,包括基因组注释、进化保守度指标和人口水平特征。特别是新引入的人群等位基因频率特征值,使得PAFA可以通过计算固定指数和离散度得分,对群体内部及群体间的差异性和多样性进行评估,从而能够在大量的背景变异中有效识别出与复杂疾病有关的功能性变异。此外,PAFA更加合理有效地对训练集进行了数据清洗。它从ClinVar、***基因组计划和GWASdb等多个权威数据库中获取训练数据,并针对不同来源的变异采取了多重过滤策略。此外,该团队构建了一个友好的在线集成平台,访问地址:http://159.226.67.237:8080/pafa。此平台不仅允许用户利用PAFA对变异进行评估,而且通过整合丰富的功能组学数据,为遗传变异提供全面的功能性注释。

通过一系列综合测评分析,PAFA无论对于编码区还是非编码区的变异,都表现出更为出色的功能评估效果。尤其是对于非编码区致病变异的识别方面,比现有方法拥有更高的敏感度和特异度。通过对不同训练特征进行留一法交叉验证,发现群体等位基因频率特征的引入,可以显着提高对非编码区致病变异的识别效率。此外,合理地整合和清洗多种训练集,将会在区分癌症相关的频发变异(recurrent variant)和非频发变异方面取得更好的效果。

该工作由赵方庆课题组的研究生周琳完成,得到了国家自然科学基金委和中国科学院的经费支持。

原始出处:
Lin Zhou,Fangqing Zhao.Prioritization and functional assessment of noncoding variants associated with complex diseases.Genome Medicine201810:53https://doi.org/10.1186/s13073-018-0565-y

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    2019-04-24 gous
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    2018-10-08 kalseyzl
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    2019-06-25 cnxcy
  4. 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createdName=kalseyzl, createdTime=Mon Oct 08 23:47:00 CST 2018, time=2018-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1718839, encodeId=06e01e188399f, content=<a href='/topic/show?id=d3e9864e750' target=_blank style='color:#2F92EE;'>#致病性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86477, encryptionId=d3e9864e750, topicName=致病性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d36132650190, createdName=cnxcy, createdTime=Tue Jun 25 20:47:00 CST 2019, time=2019-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1858885, encodeId=5e38185888535, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Tue Apr 02 04:47:00 CST 2019, time=2019-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1743471, encodeId=fede1e4347108, content=<a href='/topic/show?id=369199618db' target=_blank style='color:#2F92EE;'>#非编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99618, encryptionId=369199618db, topicName=非编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32d435134939, createdName=d830384, createdTime=Sun Jan 06 22:47:00 CST 2019, time=2019-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1922202, encodeId=ee041922202be, content=<a href='/topic/show?id=33915836275' target=_blank style='color:#2F92EE;'>#新成果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58362, encryptionId=33915836275, topicName=新成果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Thu Nov 22 22:47:00 CST 2018, time=2018-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342500, encodeId=3c681342500c6, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577615, encodeId=74fa15e76157e, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584707, encodeId=fad31584e0778, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608967, encodeId=ba70160896e3c, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
    2019-04-02 jeanqiuqiu
  5. [GetPortalCommentsPageByObjectIdResponse(id=1862638, encodeId=6850186263835, content=<a href='/topic/show?id=a121223385b' target=_blank style='color:#2F92EE;'>#中科院#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22338, encryptionId=a121223385b, topicName=中科院)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a9987, createdName=gous, createdTime=Wed Apr 24 22:47:00 CST 2019, time=2019-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1773719, encodeId=e3a91e73719aa, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9a038523631, createdName=kalseyzl, createdTime=Mon Oct 08 23:47:00 CST 2018, time=2018-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1718839, encodeId=06e01e188399f, content=<a href='/topic/show?id=d3e9864e750' target=_blank style='color:#2F92EE;'>#致病性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86477, encryptionId=d3e9864e750, topicName=致病性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d36132650190, createdName=cnxcy, createdTime=Tue Jun 25 20:47:00 CST 2019, time=2019-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1858885, encodeId=5e38185888535, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Tue Apr 02 04:47:00 CST 2019, time=2019-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1743471, encodeId=fede1e4347108, content=<a href='/topic/show?id=369199618db' target=_blank style='color:#2F92EE;'>#非编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99618, encryptionId=369199618db, topicName=非编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32d435134939, createdName=d830384, createdTime=Sun Jan 06 22:47:00 CST 2019, time=2019-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1922202, encodeId=ee041922202be, content=<a href='/topic/show?id=33915836275' target=_blank style='color:#2F92EE;'>#新成果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58362, encryptionId=33915836275, topicName=新成果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Thu Nov 22 22:47:00 CST 2018, time=2018-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342500, encodeId=3c681342500c6, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577615, encodeId=74fa15e76157e, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584707, encodeId=fad31584e0778, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608967, encodeId=ba70160896e3c, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
    2019-01-06 d830384
  6. [GetPortalCommentsPageByObjectIdResponse(id=1862638, encodeId=6850186263835, content=<a href='/topic/show?id=a121223385b' target=_blank style='color:#2F92EE;'>#中科院#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22338, encryptionId=a121223385b, topicName=中科院)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a9987, createdName=gous, createdTime=Wed Apr 24 22:47:00 CST 2019, time=2019-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1773719, encodeId=e3a91e73719aa, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9a038523631, createdName=kalseyzl, createdTime=Mon Oct 08 23:47:00 CST 2018, time=2018-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1718839, encodeId=06e01e188399f, content=<a href='/topic/show?id=d3e9864e750' target=_blank style='color:#2F92EE;'>#致病性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86477, encryptionId=d3e9864e750, topicName=致病性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d36132650190, createdName=cnxcy, createdTime=Tue Jun 25 20:47:00 CST 2019, time=2019-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1858885, encodeId=5e38185888535, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Tue Apr 02 04:47:00 CST 2019, time=2019-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1743471, encodeId=fede1e4347108, content=<a href='/topic/show?id=369199618db' target=_blank style='color:#2F92EE;'>#非编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99618, encryptionId=369199618db, topicName=非编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32d435134939, createdName=d830384, createdTime=Sun Jan 06 22:47:00 CST 2019, time=2019-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1922202, encodeId=ee041922202be, content=<a href='/topic/show?id=33915836275' target=_blank style='color:#2F92EE;'>#新成果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58362, encryptionId=33915836275, topicName=新成果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Thu Nov 22 22:47:00 CST 2018, time=2018-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342500, encodeId=3c681342500c6, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577615, encodeId=74fa15e76157e, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584707, encodeId=fad31584e0778, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608967, encodeId=ba70160896e3c, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat Jul 14 10:47:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
    2018-11-22 wgx306
  7. [GetPortalCommentsPageByObjectIdResponse(id=1862638, encodeId=6850186263835, content=<a href='/topic/show?id=a121223385b' target=_blank style='color:#2F92EE;'>#中科院#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22338, encryptionId=a121223385b, topicName=中科院)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a9987, createdName=gous, createdTime=Wed Apr 24 22:47:00 CST 2019, time=2019-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1773719, encodeId=e3a91e73719aa, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9a038523631, 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