Microbial genome sequencing

Complete genome sequences of 30 microbial species have been determined during the past five years, and work in progress indicates that the complete sequences of more than 100 further microbial species will be available in the next two to four years. These results have revealed a tremendous amount of information on the physiology and evolution of microbial species, and should provide novel approaches to the diagnosis and treatment of infectious disease.     

一类半导体器件模拟的Galerkin-MMOCAA方法

用MMOCAA格式（调整对流的特征线修正方法）处理半导体器件模拟的对流占优扩散问题,通过对对流项进行调整,仅增加少童计算量,使该问题既保持了全局质量守恒性质,又具有MMOC格式（特征线修正技术）的所有优点．进行了理论分析,得到了最优阶L^2模误差估计结果．     

An SNP map of the human genome generated by reduced representation shotgun sequencing

Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history. It has been proposed that a dense map of 30,000-500,000 SNPs can be used to scan the human genome for haplotypes associated with common diseases. Here we describe a simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps. RRS re-samples specific subsets of the genome from several individuals, and compares the resulting sequences using a highly accurate SNP detection algorithm. The method can be extended by alignment to available genome sequence, increasing the yield of SNPs and providing map positions. These methods are being used by The SNP Consortium, an international collaboration of academic centres, pharmaceutical companies and a private foundation, to discover and release at least 300,000 human SNPs. We have discovered 47,172 human SNPs by RRS, and in total the Consortium has identified 148,459 SNPs. More broadly, RRS facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species. SNPs discovered by RRS also offer unique advantages for large-scale genotyping.     

便携式半导体激光器特性参数测试仪的研制

研制一种基于单片机控制的便携式半导体激光器特性参数测试仪.该仪器由硬件测试电路和上层软件测试系统组成,能够测试各种封装形式的LD电特性参数和特性曲线.包括自动电流控制(ACC)、自动电压控制(AvC)、自动功率控制(APC)和自动背向光电流控制(AMC)四种驱动方式;包括集成的温控电路,能够快速精确控制LD工作温度;保护电路可以使LD免受浪涌冲击等损害;上层软件系统可以很直观绘制LD的各种特性曲线.测试系统还具有体积小、携带方便、操作简单等优点.     

Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.     

Melanoma genome sequencing reveals frequent PREX2 mutations

Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.     

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.     

Mapping copy number variation by population-scale genome sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.     

Controllable growth of dielectric/semiconductor integrated films

Currently, electronic information systems are developing quickly towards further miniaturization and monolithic integration so as to realize smaller volume, higher velocity and lower power consumption. For this purpose, the integration of all sorts of active devices （mainly fabricated by semiconductors） with passive devices （fabricated by functional materials） is particularly important and impendent. Therefore, it is necessary to integrate multifunctional oxide dielectrics possessing electric, magnetic, acoustic, optical and thermal properties characterized by spontaneous polarization with semiconductors bearing the characters of carrier transportation to form artificial structures via deposition of solid films. This kind of integrated films may have two characters, i.e., the all-in-one multifuncUon and modulation of electromagnetic properties by hetero-interface. This makes it possible to realize monolithic integration of detecting, processing, transmission, executing and storing of electronic information. Meanwhile, possible integrated coupling effects will be pursued instead of exploring the limited physical properties of the related materials. In this paper, we put forward a new direction of developing electronic devices with higher performances, and demonstrate some results concerning our recent research on the interface-controllable integrated growth of dielectrics and GaN. Recent progresses of the related research in the world are also reviewed.     

Enhancing semiconductor device performance using ordered dopant arrays

As the size of semiconductor devices continues to shrink, the normally random distribution of the individual dopant atoms within the semiconductor becomes a critical factor in determining device performance--homogeneity can no longer be assumed. Here we report the fabrication of semiconductor devices in which both the number and position of the dopant atoms are precisely controlled. To achieve this, we make use of a recently developed single-ion implantation technique, which enables us to implant dopant ions one-by-one into a fine semiconductor region until the desired number is reached. Electrical measurements of the resulting transistors reveal that device-to-device fluctuations in the threshold voltage (Vth; the turn-on voltage of the device) are less for those structures with ordered dopant arrays than for those with conventional random doping. We also find that the devices with ordered dopant arrays exhibit a shift in Vth, relative to the undoped semiconductor, that is twice that for a random dopant distribution (- 0.4 V versus -0.2 V); we attribute this to the uniformity of electrostatic potential in the conducting channel region due to the ordered distribution of dopant atoms. Our results therefore serve to highlight the improvements in device performance that can be achieved through atomic-scale control of the doping process. Furthermore, ordered dopant arrays of this type may enhance the prospects for realizing silicon-based solid-state quantum computers.     

A map of human genome variation from population-scale sequencing

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.     

Initial sequencing and comparative analysis of the mouse genome

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.     

Initial impact of the sequencing of the human genome

The sequence of the human genome has dramatically accelerated biomedical research. Here I explore its impact, in the decade since its publication, on our understanding of the biological functions encoded in the genome, on the biological basis of inherited diseases and cancer, and on the evolution and history of the human species. I also discuss the road ahead in fulfilling the promise of genomics for medicine.     

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.     

掺杂磁垒纳米结构中的GMR效应及调控

通过在半导体异质结上的上下表面沉积两条平行的铁磁条带可获得一个巨磁阻器件.为了更好地调控其性能,我们从理论上研究了在该器件中加入δ势后,该器件的透射系数、电导和磁阻比率的变化情况.研究发现,加入δ势后,该器件同样具有明显的巨磁阻效应,且其磁阻比率与加入δ势的权重和位置密切相关.因此,我们可以通过改变加入δ势的权重和位置来调控该巨磁阻器件,设计出磁阻比率可调的磁信息存储器.     

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.     

海神单胞菌属的基因组测序数据分析

海神单胞菌属(Neptunomonas)于1999年被首次鉴定,目前包含8个菌种,其中6个已经完成全基因组测序。本文总结了海神单胞菌属的菌种特征和基因组信息,并利用基因组测序数据对该菌属的碳源利用途径、聚羟基脂肪酸酯代谢途径和芳香族化合物降解途径进行了分析。研究发现,海神单胞菌属具有完整的糖酵解和乙酸利用途径,普遍含有Ⅰ型和Ⅲ型的聚羟基脂肪酸酯合成酶,存在芳香族化合物的降解途径。基因组测序数据分析结果可以为海神单胞菌属在聚羟基脂肪酸酯合成与环境治理保护等领域的应用提供理论依据。