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我国科研人员开发深度学习超分辨显微成像方法并应用于细胞器互作网络研究

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发布时间：2021-08-25

来源：酯香香化学采购网

【化工仪器网科技前沿】

　　图1：基于DFCAN和DFGAN结构光超分辨重建活细胞内的线粒体内膜结构(绿色)和内质网(紫红色)，捕捉到线粒体在内质网与线粒体接触位点线粒体融合的动态过程

　　在国家自然科学基金重大研究计划“细胞器互作网络及其功能研究”(批准号：91754202)资助下，中国科学院生物物理研究所李栋研究员课题组与清华大学戴琼海教授合作，从多个维度综合分析了现有超分辨卷积神经网络模型对于显微图像的超分辨性能，并将基于DFCAN深度学习算法的结构光超分辨显微镜系统(DFCAN-SIM)运用于观测线粒体内脊、线粒体拟核、内质网、微丝骨架等细胞器的动态互作新行为。相关成果以“超分辨卷积神经网络模型对于显微图像的超分辨性能综合分析与方法发展(Evaluation and development of deep neural networks for image super-resolution in optical microscopy)”为题，于2021年1月21日在《Nature Methods》(《自然方法学》)在线发表。

　　传统的细胞生物学研究大多以静态观察为主，关注细胞器独立执行功能时的结构和分子机制。近年来，随着生物学研究方法的发展，特别是荧光显微成像技术的进步，越来越多的细胞生物学研究逐步揭示功能各异的细胞器之间通过不同细胞器间膜接触(membrane contact)协同执行生命活动的新机制，而且细胞器互作的动态变化对于维持细胞器的稳态平衡、调控其动态变化起着重要的作用。高分辨率条件下实时记录并绘制细胞器动态互作是精确揭示细胞器互作功能及其分子机制的基础。这对目前的显微成像技术提出了更高的要求，亟需发展适于对活细胞进行多色高速超分辨成像的系统来推进细胞器互作领域的研究。

　　李栋课题组在以往超分辨显微系统研制的基础上，进一步发展出多模态结构光照明超分辨显微镜系统(Multimodality Structured Illumination Microscopy，Multi-SIM)，并与清华大学戴琼海课题组合作采集了可用于深度学习模型训练的高质量公开数据集BioSR，并提出测评矩阵(assessmentmatrix)方法，从多个维度综合分析了现有超分辨卷积神经网络模型对于显微图像的超分辨性能，在此基础上，课题组深度挖掘图像超分辨过程中的频域特征，提出了傅立叶域注意力卷积神经网络(Deep Fourier Channel Attention Network, DFCAN)。相较于其它超分辨卷积神经网络，DFCAN可以在不同成像条件下实现优的显微图像超分辨预测和结构光超分辨图像重建效果，依据测评矩阵结果，其优越区域可以拓展至中、高信噪比成像条件，可在实际生物成像实验中替代现有超分辨成像方法，大大提升了深度学习超分辨成像方法的性能。

　　李栋课题组将基于DFCAN深度学习算法的结构光超分辨显微镜系统(DFCAN-SIM)成功运用于观测线粒体内脊、线粒体拟核、内质网等细胞器的动态互作新行为。例如：在低激发功率的成像条件下对COS-7细胞中的线粒体内膜和线粒体拟核进行活细胞双色成像，成像时程(>1000张超分辨图像)达到传统活细胞超分辨成像方法的10倍以上，并成功观察到伴随着线粒体内脊形变的拟核分离和聚合现象，提示在动物细胞内，线粒体内脊的形变可能调控着线粒体拟核的分布和形态。此外，他们还观察到在活细胞中环形线粒体会在细胞质流的推动下进行双向旋转，暗示动物细胞一定程度上，也有与植物细胞类似的涡旋细胞质流调节胞内稳态。这些新发现表明DFCAN-SIM能够在更低信噪比成像条件下获得与传统超分辨显微镜技术媲美的成像效果，从而扩大了传统超分辨成像技术的适用范围，并为超分辨光学显微成像技术的进一步发展开拓新的技术路径。

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[ SQL ] SHOW COLUMNS FROM `yzn_poster` [ RunTime:0.001030s ]
[ SQL ] SELECT * FROM `yzn_poster` WHERE `cate_id` = 99 AND `p_c_id` = 52 AND `status` = 1 LIMIT 1 [ RunTime:0.000348s ]
[ SQL ] SELECT * FROM `yzn_poster` WHERE `cate_id` = 99 AND `p_c_id` = 55 AND `status` = 1 LIMIT 1 [ RunTime:0.000208s ]
[ SQL ] SHOW COLUMNS FROM `yzn_goods_property` [ RunTime:0.001188s ]
[ SQL ] SELECT `g`.`name`,`p`.`price`,`p`.`unit`,`p`.`type`,`p`.`thumb`,p.id as p_id,`p`.`value`,`p`.`is_where`,`p`.`sku_unit`,`p`.`repeat_type`,`p`.`goods_id` FROM `yzn_goods_property` `p` LEFT JOIN `yzn_goods` `g` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `p`.`recommend` = 1 GROUP BY `p`.`goods_id`,`p`.`repeat_type` ORDER BY `p`.`sort` DESC,`g`.`id` DESC LIMIT 0,15 [ RunTime:0.002372s ]
[ SQL ] SHOW COLUMNS FROM `yzn_goods_category` [ RunTime:0.000837s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `hot_search` = 1 AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000379s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `is_show` > 0 AND `status` = 1 ORDER BY `listorder` ASC [ RunTime:0.000253s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `id` IN (1,2,7,16,17,34,92,95,38) [ RunTime:0.000231s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 1 AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000177s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 2 AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000155s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 7 AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000167s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 16 AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000172s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 17 AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000151s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` IN (34,92) AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000158s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` IN (95,38) AND `status` = 1 ORDER BY `listorder` ASC,`id` DESC [ RunTime:0.000224s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 1 AND `status` = 1 [ RunTime:0.000167s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` = 1 [ RunTime:0.000151s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,1,%' ) [ RunTime:0.000156s ]
[ SQL ] SHOW COLUMNS FROM `yzn_goods` [ RunTime:0.000599s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (25,26,29,30,48,1) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000938s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 2 AND `status` = 1 [ RunTime:0.000189s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` = 2 [ RunTime:0.000156s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,2,%' ) [ RunTime:0.000162s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (42,43,2) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000914s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 7 AND `status` = 1 [ RunTime:0.000190s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` = 7 [ RunTime:0.000153s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,7,%' ) [ RunTime:0.000182s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (10,14,32,33,49,50,51,52,53,54,55,56,57,58,96,97,7) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000989s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 16 AND `status` = 1 [ RunTime:0.000187s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` = 16 [ RunTime:0.000157s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,16,%' ) [ RunTime:0.000163s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (59,60,61,62,63,16) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000875s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 17 AND `status` = 1 [ RunTime:0.000172s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` = 17 [ RunTime:0.000154s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,17,%' ) [ RunTime:0.000147s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (40,64,65,66,67,68,100,17) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000854s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 34 AND `status` = 1 [ RunTime:0.000190s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 92 AND `status` = 1 [ RunTime:0.000169s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` IN (34,92) [ RunTime:0.000183s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,34,%' or arrparentid like '0,92,%' ) [ RunTime:0.000169s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (35,70,71,93,94,34,92) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000843s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 95 AND `status` = 1 [ RunTime:0.000169s ]
[ SQL ] SELECT `id`,`catname` FROM `yzn_goods_category` WHERE `pid` = 38 AND `status` = 1 [ RunTime:0.000141s ]
[ SQL ] SELECT * FROM `yzn_goods_category` WHERE `status` = 1 AND `id` IN (95,38) [ RunTime:0.000183s ]
[ SQL ] SELECT `id` FROM `yzn_goods_category` WHERE `status` = 1 AND ( arrparentid like '0,38,%' or arrparentid like '0,95,%' ) [ RunTime:0.000169s ]
[ SQL ] SELECT `g`.`name`,p.id as p_id,`p`.`price`,`p`.`type`,`p`.`thumb`,`p`.`unit`,`p`.`is_where`,`p`.`goods_id`,`p`.`repeat_type` FROM `yzn_goods` `g` LEFT JOIN `yzn_goods_property` `p` ON `p`.`goods_id`=`g`.`id` WHERE `p`.`status` = 1 AND `p`.`is_del` = 0 AND `g`.`is_del` = 0 AND `p`.`is_where` LIKE '%1%' AND `g`.`cate_id` IN (47,74,75,76,77,78,79,80,81,82,83,99,95,38) AND `p`.`hot_sale` = '1' GROUP BY `p`.`repeat_type`,`p`.`goods_id` ORDER BY `p`.`sort` DESC,`p`.`id` DESC LIMIT 0,10 [ RunTime:0.000839s ]
[ SQL ] SHOW COLUMNS FROM `yzn_article` [ RunTime:0.000894s ]
[ SQL ] SELECT `A`.*,`AD`.*,`C`.`catname` FROM `yzn_article` `A` INNER JOIN `yzn_article_data` `AD` ON `A`.`id`=`AD`.`did` INNER JOIN `yzn_category` `C` ON `C`.`id`=`A`.`catid` WHERE `A`.`id` = 5551 AND `A`.`status` = 1 LIMIT 1 [ RunTime:0.000509s ]
[ SQL ] SHOW COLUMNS FROM `yzn_category` [ RunTime:0.000538s ]
[ SQL ] SELECT `id` FROM `yzn_category` WHERE `parentid` = 35 AND `status` = 1 [ RunTime:0.000158s ]
[ SQL ] SELECT `id` FROM `yzn_category` WHERE `parentid` IN (36,37,38,39,40,41,42) AND `status` = 1 [ RunTime:0.000158s ]
[ SQL ] SELECT `id` FROM `yzn_category` WHERE `parentid` = 43 AND `status` = 1 [ RunTime:0.000135s ]
[ SQL ] SELECT `id` FROM `yzn_category` WHERE `parentid` IN (44,45,46,47,48,49,50) AND `status` = 1 [ RunTime:0.000137s ]
[ SQL ] SELECT `id` FROM `yzn_category` WHERE `parentid` = 6 AND `status` = 1 [ RunTime:0.000124s ]
[ DB ] CONNECT:[ UseTime:0.000295s ] mysql:host=127.0.0.1;port=3306;dbname=yzncms;charset=utf8
[ SQL ] SELECT `A`.`id`,`A`.`title` FROM `yzn_article` `A` INNER JOIN `yzn_category` `C` ON `C`.`id`=`A`.`catid` WHERE `A`.`status` = 1 AND `A`.`catid` IN (35,36,37,38,39,40,41,42) ORDER BY `A`.`flag` DESC,`A`.`listorder` ASC,`A`.`updatetime` DESC [ RunTime:0.022358s ]
[ SQL ] UPDATE `yzn_article` SET `hits` = `hits` + 1 WHERE `id` = 5551 [ RunTime:0.000390s ]
[ SQL ] SELECT * FROM `yzn_poster` WHERE `cate_id` = 10 AND `p_c_id` = 41 ORDER BY `listorder` ASC LIMIT 4 [ RunTime:0.000439s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `yzn_article` `a` INNER JOIN `yzn_category` `c` ON `a`.`catid`=`c`.`id` WHERE `catid` = 38 AND `a`.`status` = 1 [ RunTime:0.002851s ]
[ SQL ] SELECT `a`.*,`c`.`catname` FROM `yzn_article` `a` INNER JOIN `yzn_category` `c` ON `a`.`catid`=`c`.`id` WHERE `catid` = 38 AND `a`.`status` = 1 ORDER BY `flag` DESC,`listorder` ASC,`updatetime` DESC LIMIT 0,6 [ RunTime:0.004818s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `yzn_article` `a` INNER JOIN `yzn_category` `c` ON `a`.`catid`=`c`.`id` WHERE `catid` = 37 AND `a`.`status` = 1 [ RunTime:0.002733s ]
[ SQL ] SELECT `a`.*,`c`.`catname` FROM `yzn_article` `a` INNER JOIN `yzn_category` `c` ON `a`.`catid`=`c`.`id` WHERE `catid` = 37 AND `a`.`status` = 1 ORDER BY `flag` DESC,`listorder` ASC,`updatetime` DESC LIMIT 0,6 [ RunTime:0.005086s ]