BioSun:计算机辅助分子生物学实验设计的软件系统

论述了我们自行研究与开发的分子生物学实验辅助设计的生物信息学软件系统BioSun。该系统运行于Windows环境，其主要功能有：可视化的序列编辑、可接收多种序列格式(EMBL，GenBank和FastA)的数据库管理系统、多种方式的序列比较、多种方式的抗原表位预测、基于多种算法的RNA二级结构预测、酶切位点分析及酶切图谱制作、PCR实验辅助设计、辅助寡核苷酸微阵列的探针设计、辅助cDNA微阵列的引物设计和原核系统外源基因高效表达设计等。BioSun系统使用图形用户界面方式，可实现对图形与文本文件的灵活管理，具有操作灵活、功能多样等特点，可用于分子生物学实验的辅助设计，对加快实验进程和提高实验的成功率具有重要意义。     

TXT2DNA：基于DNA序列的文本编、解码及比对软件系统

TXT2DNA是由我们实验室新近设计完成的一个能够将汉字等文本信息编码为DNA序列并可将后者解码还原为文本信息,同时可提供基于DNA序列比对技术的文本数据分析软件系统。TXT2DNA通过建立包括汉字字符在内的多种语言字符与DNA序列之间的唯一对应关系,为每个字符分配Unicode（唯一序列码）,实现从文字字符到DNA序列的编码与解码功能,进而实现了DNA与汉字字符的互通。     

E型肉毒神经毒素(BoNT)基因序列分析及其B细胞表位预测

目的：分析不同E型肉毒梭菌的肉毒神经毒素（BoNT）基因序列的同源性，预测E型BoNT的B细胞表位。方法：用LaserGene软件中的MegAlign程序比对GenBank中5株不同E型肉毒梭菌的BoNT基因序列；分别利用BioSun和LaserGene软件分析E型BoNT的表位参数、蛋白质二级结构及氨基酸序列保守性，利用三维结构显示软件Cn3D，分析E型BoNT可能的B细胞表位的空间定位，进而预测E型BoNT的B细胞表位。结果：5个E型BoNT基因核酸序列同源性为97．2％-100％，氨基酸序列同源性为95％-100％；E型BoNT轻链中的62-78，111-127区段，重链中443-465，661-677，693～709，727-743，853-869，1093-1109，1128-1144，1163-1179区段最有可能是其B细胞优势表位。结论：我们利用不同分析软件，结合多参数综合预测出了E型BoNT的多个B细胞表位，为进一步鉴定E型BoNer的B细胞表位及其多表位疫苗的研究奠定了基础。     

基于MR三维梯度回波与扩散加权成像序列的脑表面重组技术比较

目的 使用MR三维梯度回波（3D flash）序列和扩散加权成像（DWI）序列的扫描图像进行脑表面三维重组，对两种方法显示脑表面结构的能力、价值与限度及临床应用等进行比较和探讨。方法 对30名正常人行头颅3D flash和DWI检查。通过容积重组显示脑表面解剖结构。同一组医生对两种方法重组图像进行评价和评分，并比较结果。结果 基于3D flash重组的各脑表面结构清楚显示，平均得分均在2．50分以上。基于DWI的重组图像能够较好地显示中央前回、中央后回、顶上小叶、额上回、中央前沟、中央沟、中央后沟、顶间沟及额上沟等结构，平均得分2．60～2．75分，缘上回、角回、额中回、额下回、颞上回、外侧沟和额下沟等结构显示较差，平均得分1．67～2．48分，颞中回、颞下回、颞上沟及颞下沟等显示很差，平均得分仅0．88～1．27分。比较两种方法的平均得分，基于3D flash重组优于基于DWI的三维重组，差异有统计学意义，P值均〈0．01。结论 基于3D flash重组能够显示真实的脑表面主要脑沟、脑回和脑裂，对脑解剖形态的研究和定位诊断有重要意义。基于DWI的三维脑表面重组能比较满意地显示顶叶、额叶的主要表面结构，扫描和重组快速，有一定实用价值。     

生物信息与生物医学的研究

介绍生物信息资料数据库近年来的发展和生物信息数据库在生物医学研究中的几个主要应用方面:(1)选择实验研究的技术途径,找出最佳实验条件;(2)预测序列的各种功能位点、结构域和高级结构;(3)对序列的理论分析。同时也简要地指出序列分析软件的主要发展趋势。     

计算机视频图象处理技术在动态生物医学图象研究中的应用

动态序列图象能够充分描述运动过程的特性与规律，但因数据量极大，分析研究具有一定的难度。我们将微机图象处理系统与视频摄录像设备结合，利用视频图象２４帧／秒的时序性，建立了一种动态生物医学图象处理分析系统，并运用该系统的对人体颈椎的三维运动过程和人体行走足底动态应力分布进行了测试分析，取得了良好结果，为生物医学中人体运动功能的定量检测、描述，体育运动的分析、评价，以及运动伤病的治疗与康复研究提供了一种新的有效途径。     

3D-重T_2W水成像技术显示面听神经及内耳结构的研究

目的：探讨MR薄层3D-重T2W水成像技术对内听道面听神经分支和迷路解剖结构的显示情况。方法：选择40例(80侧)无耳部疾病患者，使用GE Signal．5T超导MR成像仪，头部环形线圈或3in(7．62cm)环形线圈，0．5mm层厚3IL重T2WIFSE序列与常规T2WIFSE序列对两例子部同时进行扫描，比较两者对内听道面听神经分支和迷路解剖结构的显示率，并作统计分析。结果：3D-重T2WIFSE序列与常规T2WIFSE序列对其细微结构的显示率分别为螺旋板(98％：0％，P＜0．01)、前庭阶(98％：0％，P＜0．01)、鼓阶(98％：0％，P＜0．01)、椭圆囊(95％：0％，P＜0．01)、球囊(95％：0％，P＜0．01)、前庭嵴(95％：0％，P＜0．01)、前庭上神经(100％：40％，P＜0．01)、前庭下神经(98％：20％，P＜0．01)，其差异均有显著性意义，而在3个半规管、前庭、耳蜗、内听道面神经、蜗神经等结构的显示率方面差异无显著性意义(P＞0．05)。结论：薄层3D-重T2WFSE水成像技术在显示内听道前庭上下神经分支和迷路的螺旋板、前庭阶、鼓阶、椭圆囊、球囊等细微结构方面明显优于常规T2WI。     

不同场强和序列的超顺磁性氧化铁磁共振增强扫描在肝癌检出中的比较

比较不同的场强和扫描序列对超顺磁性氧化铁增强前后肝癌检出的影响。材料和方法：46例104个肝癌病灶在1．0T或1．5T场强下行磁共振T1加权及四个T2加权的平扫及SPIO增强扫描，比较不同场强下各扫描序列的信噪比、对比噪声比以及肝癌病灶的检出率。结果：SPIO增强扫描后，所有序列的信噪比均下降，但对比噪声比和肝癌检出率均增加。1．0T场强下，最佳的SPIO增强序列为SE和TSE的T2加权；1．5T场强下最佳的SPIO增强序列为HASTE和FS－HASTE的T2加权。结论：不同场强下最合适SPIO增强扫描的都是信噪比较好的、中等权重的T2加权序列，1．5T更适合屏气的快速序列，1．0T更适合非屏气的SE序列。     

西尼罗病毒Chin-01株基因组编码区序列测定及分析

目的：对保存的西尼罗病毒Chin-01株基因组编码区序列进行测定，了解其与已报道毒株的序列差异及系统进化关系。方法：对Chin-01株病毒基因组编码区分区段进行RT-PCR扩增，分别将扩增产物直接进行测序，采用DNAstar软件将测序片段拼接获得全长编码区序列。结果与结论：Chin-01株基因组编码区全长10302nt，为单一读码框架，编码3434个氨基酸。其中结构蛋白基因为2373nt，依次编码4种结构蛋白(C，PrM，M和E)；非结构蛋白基因全长7926nt，依次编码7种非结构蛋白(NS1，NS2a，NS2b，NS3，NS4a，NS4b和NS5)。序列同源性分析表明，Chin-01株与埃及Eg101株高度同源，两者氨基酸序列仅有0．3％的差异。该株西尼罗病毒基因组编码区序列已输入GenBank数据库。     

一低剂量辐射诱导新基因的转录调控和初步功能分析

目的：克隆低剂量辐射诱导基因，研究辐射对其转录调控作用和生物学功能。方法：用mRNA差异显示技术分离辐射诱导表达基因，用RACE技术获取cDNA旁侧序列，Northern杂交分析基因的转录调节，生物信息学分析基因的结构和功能。结果：获得包括3'端在内的辐射诱导新基因LRIGx的cDNA片段，序列同源性比较显示与人染色体20ql 1.2-12一段DNA高度同源（＞99％），Northern杂交结果揭示该基因转录子全长约8．5kb，在0．2Gy照射后2h出现诱导表达，4h后转录子水平为对照细胞的5倍多，也受0．02Gy更低剂量照射诱导表达，2Gy大剂量照射后1h出现短暂诱导表达，但不如低量照射明显，2h后恢复正常水平，生物信息学分析结果显示该基因编码产物含有解旋酶活性保守区，结论：分离鉴定出一低剂量辐射反应基因，其编码蛋白可能参与DNA代谢（如修复）等细胞辐射反应过程。     

乳腺生长抑制因子mammastatin表位抗原的克隆表达及初步血清学测定

目的:获得重组乳腺生长抑制因子(mammastatin)表位抗原蛋白,制备抗血清,以测定正常人及乳腺癌患者血清中mammastatin存在水平.方法:用BioSun生物软件对 mammastatin氨基酸序列进行分析,确定表位序列,PCR逐步延伸法合成表位基因,构建pBVIL1-mammastatin和pBVIL6-mammastatin表达质粒,转化于大肠杆菌HB101中进行表达,经纯化后免疫大耳白兔,制备抗血清,用双抗体夹心法检测乳腺癌及正常人的血清.结果:重组 mammastatin抗原在大肠杆菌中获得了高效表达,并获得了兔多抗血清.用双抗体夹心法检测,显示95例正常对照血清mammastatin表达水平显著高于95例乳腺癌(平均D值,正常组0.261,乳腺癌组0.135,Wilcoxon秩和检验P=0.000<0.01,差异显著).结论:正常人血清中乳腺生长抑制因子mammastatin 存在水平显著高于乳腺癌患者.     

利用Galaxy与高性能计算集群构建本地化一站式生物信息学平台

目的构建本地化的高性能一站式数据分析平台,为生物医学研究的相关科研人员提供便捷高效的计算分析服务。方法将Galaxy软件部署在计算集群上,集成工具软件和数据集;利用分布式资源管理应用接口（DRMAA）实现与SunGridEngine的协同运作,自动调度和分配计算资源;并在集群上构建稳定的weh服务、FrP服务和管理数据库。结果该平台已投入试运行并在不断完善,峰值计算能力达到每秒lO万亿次,存储容量为40TB,提供序列比对、短串映射、基因注释、转录组分析、宏基因组分析及进化分析等多种功能,以及容量约为700GB的人类基因组、病毒、细菌、真菌等参考数据库。结论该平台具备大规模数据分析的能力,能够解决高通量测序所带来的海量生物数据的存储与处理等问题。与在普通服务器上进行数据分析相比,该平台的计算集群能极大地加快数据处理过程,提高研究效率。     

Extension of the UNFOLD method to include free breathing.

Unaliasing by Fourier-encoding the overlaps using the temporal dimension (UNFOLD) is a method to reduce the data acquisition burden in dynamic MRI. The method works by forcing aliased signals to behave in specific ways through time, so that these unwanted signals can be detected and removed. Unexpected events in time, such as displacements caused by breathing, have the potential to disturb the temporal strategy and may affect UNFOLD's ability to suppress aliasing artifacts. This work presents an extension of the UNFOLD method to accommodate temporal encoding disruptions. While the main type of disruption considered here comes from respiratory motion, other types of disruption can be envisioned, such as departures from the usual UNFOLD k-space sampling scheme. This extended version of UNFOLD was incorporated into UNFOLD-sensitivity encoding (UNFOLD-SENSE), and should also be applicable to closely related methods such as temporal SENSE (TSENSE), k-t Broaduse Linear Acquisition Speed up Technique (k-t BLAST), and k-t SENSE. Five patients were imaged with a modified version of a myocardial-perfusion sequence, and UNFOLD was used either alone or in conjunction with SENSE to obtain an acceleration of 2.0 (in three patients) or 3.0 (in two patients). In both cases this extended version of UNFOLD was able to suppress artifacts caused by the presence of breathing motion.     

生物医学数据处理机的研制

本文论述了一种以国产单板机为基础,通过软、硬件扩展设计研制而成的医用数据处理机。该机具有多种功能,尤其适用于诱发生物电信号的分析处理,造价低廉,操作方便,工作稳定可靠。     

Software control procedures for treatment planning systems

In radiotherapy treatment planning systems, the software programs as well as the beam data have to be updated frequently, when new software versions are released or as beam data change. This update procedure has to be carried out carefully, to ensure the integrity of the system software and data. Moreover, the version of software used for a particular patient treatment plan is important, not only as a record to be retrieved when necessary, but also when there are multiple terminals connected to the same computer. This process of version control is not always carried out in a systematic and standardized fashion. Most clinics often have their own systems to implement this procedure, but while some systems are comprehensive, others may not necessarily incorporate enough safeguards for errors. In addition, treatment planning system manufacturers often do not offer well-designed and fail-safe facilities for this important issue. This report describes the software update control procedures we have implemented on our treatment planning system as well as suggests some general principles that could be applied to other planning systems.     

生物医学专题信息跟踪与服务系统的设计与实现

目的构建网络化的生物医学专题信息跟踪与服务系统,为科学研究和领导决策提供信息支持。方法以MyEclipse6.5、Mysql5.1、Tomcat6.0为开发工具,以J2EE轻型构架为技术支撑,应用网络爬虫、全文检索、信息推送等技术实现系统的各项功能。结果和结论生物医学专题信息跟踪与服务系统实现了对互联网上的生物安全等专题信息进行跟踪、抓取、转换、分类和入库,以及信息的快速发布、分类导航、全文检索和个性化服务,能够主动、及时地为用户提供最新的生物医学专题信息。     

Noise reduction in multi-slice arterial spin tagging imaging.

Attenuating the static signal in arterial spin tagging (ASSIST) was initially developed for 3D imaging of cerebral blood flow. To enable the simultaneous collection of cerebral blood flow and BOLD data, a multi-slice version of ASSIST is proposed. As with the 3D version, this sequence uses multiple inversion pulses during the tagging period to suppress the static signal. To maintain background suppression in all slices, the multi-slice sequence applies additional inversion pulses between slice acquisitions. The utility of the sequence was demonstrated by simultaneously acquiring ASSIST and BOLD data during a functional task and by collecting resting-state ASSIST data over a large number of slices. In addition, the temporal stability of the perfusion signal was found to be 60% greater at 3 T compared to 1.5 T, which was attributed to the insensitivity of ASSIST to physiologic noise.     

VERIDOS: A New Tool for Quality Assurance for Intensity Modulated Radiotherapy

BACKGROUND: The use of intensity modulated radiation fields needs an extended quality assurance concept. This consists of a linac related part and a case related part. Case related means the verification of an individual treatment plan, optimized on a CT data set of an individual patient and prepared for the treatment of this patient. This part of the quality assurance work is usually time consuming, delivers only partially quantitative results and is uncomfortable without additional help. It will be shown in this paper how the software VERIDOS will improve the optimization of the case related part of the quality assurance work. MATERIAL AND METHODS: The main function of the software is the quantitative comparison of the calculated dose distribution from the treatment planning software with the measured dose distribution of an irradiated phantom. Several additional functions will be explained. Two self-developed phantoms made of RW3 (solid water) and GAFCHROMIC films or Kodak EDR2 films for the measurement of the dose distributions were used. VERIDOS was tested with the treatment planning systems Helay-TMS and Brainscan. RESULTS: VERIDOS is a suitable tool for the import of calculated dose matrices from the treatment planning systems Helax-TMS and Brainscan and of measured dose matrices exported from the dosimetry software Mephysto (PTW). The import from other treatment planning systems and scanning software applications for film dosimetry is generally possible. In such case the import function has to be adapted to the special header of the import matrix. All other functions of this software tool like normalization (automatically, manually), working with corrections (ground substraction, factors), overlay/comparison of dose distributions, difference matrix, cutting function (profiles) and export functions work reliable. CONCLUSIONS: VERIDOS improves the optimization of the case related part of the quality assurance work for intensity modulated radiation therapy (IMRT). The diverse functions of the software offer the radiation physicist a wide base to verify the IMRT plan independent from the mode of its delivery (compensator technology or MLC technology).     

Comparison of fat-suppressed T2-weighted fast spin-echo sequence and modified STIR sequence in the evaluation of the rotator cuff tendon

OBJECTIVE: This study was performed to determine whether a modified version of the classic STIR sequence provides similar information about the integrity of the rotator cuff tendon as the commonly used fat-suppressed T2-weighted fast spin-echo sequence. SUBJECTS AND METHODS: Sixty-one consecutive MRI examinations of the shoulder in 57 patients were performed using a coronal oblique T1-weighted spin-echo sequence, a modified version of the STIR sequence, and a fat-suppressed T2-weighted fast spin-echo sequence. Three reviewers independently assessed the rotator cuff tendon using the coronal oblique modified inversion recovery sequence and T1-weighted spin-echo sequence. After a minimum of 4 weeks, reviewers assessed the rotator cuff tendon using the fat-suppressed T2-weighted fast spin-echo sequence and T1-weighted spin-echo sequence. The kappa statistic was used to measure the degree of concordance between interpretations when each sequence was used independently. The conditional probability that a full- and a partial-thickness tear would be diagnosed on both sequences was calculated. Image quality was assessed in a side-by-side comparison. RESULTS: The overall weighted kappa score was 0.82, which indicates excellent concordance between the two sequences. If a full-thickness tear of the rotator cuff tendon was found on the fat-suppressed T2-weighted fast spin-echo sequence, there was a 94.1% probability that the same conclusion would be reached using the modified inversion recovery sequence. If a partial-thickness tear was found on the fat-suppressed T2-weighted fast spin-echo sequence, there was an 80.3% probability that the same conclusion would be reached with the modified inversion recovery sequence. Fat suppression in the modified inversion recovery sequence was superior to that in the T2-weighted fast spin-echo sequence in 26-39% of the examinations. CONCLUSION: The modified inversion recovery sequence and fat-suppressed T2-weighted fast spin-echo sequence provide similar information about the integrity of the rotator cuff tendon.