Genome Research：研究生发现更全面染色体测序方法
而在蛋白质测序方面，《The Scientists》杂志回顾了一下研究进展，文中提到，上个世纪70年代的生化学家在钻研细胞信号传递、循环和粘附的蛋白化学
比如，在人类破译干扰素结构之前的20多年中，很难对其进行纯化；血管紧缩素II（angiotensin II ，8个氨基酸）和抗利尿激素后叶加压素（vasopressin，9个氨基酸）等小分子，产生令人难以破译的蛋白信号。
生化学家不断提高连接、切割、提取和测序肽段的灵敏度。1950年，Pehr Edman设计出一种测序氨基酸的化学降解过程，并于1967年设计出相应的自动“测序仪”。波士顿大学Richard Laursen于1971年通过将样品固定在树脂支承上，对改良Edman设备。这种模型能够用于分析小肽，但过程中的液体溶剂会破坏样品，使稀有和分子量低的肽很难被捕捉到。
1977年，加利福尼亚理工学院生化学家William J. Dreyer发明出这里我们所见到的测序仪器。他们为玻璃管（Glass Cartridge）反应器配备了大孔性支承以固定肽段。液体和气体试剂如苯异硫氰酸酯(phenylisothiocyanate)和三甲胺(trimethylamine)气体，流过反应室与肽链的末端残基集合。经过洗涤后，气态形式的三氟乙酸（Trifluoroacetic Acid）切下残基，切下部分被苯萃取。烘干阶段，惰性气体（氮气）辅助预防样本丢失。该设备非常灵敏，几乎能计数离子。
原始出处:
Published online before print June 13, 2007, 10.1101/gr.5894107
Genome Res. 17:1101-1110, 2007
Diploid genome reconstruction of Ciona intestinalis and comparative analysis with Ciona savignyi
Jong Hyun Kim1,4, Michael S. Waterman2,3, and Lei M. Li2,3
1 Department of Computer Science, Yonsei University, Seoul, 120-749, Republic of Korea; ; 2 Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA; ; 3 Department of Mathematics, University of Southern California, Los Angeles, California 90089, USA
One of the main goals in genome sequencing projects is to determine a haploid consensus sequence even when clone libraries are constructed from homologous chromosomes. However, it has been noticed that haplotypes can be inferred from genome assemblies by investigating phase conservation in sequenced reads. In this study, we seek to infer haplotypes, a diploid consensus sequence, from the genome assembly of an organism, Ciona intestinalis. The Ciona intestinalis genome is an ideal resource from which haplotypes can be inferred because of the high polymorphism rate (1.2%). The haplotype estimation scheme consists of polymorphism detection and phase estimation. The core step of our method is a Gibbs sampling procedure. The mate-pair information from two-end sequenced clone inserts is exploited to provide long-range continuity. We estimate the polymorphism rate of Ciona intestinalis to be 1.2% and 1.5%, according to two different polymorphism counting schemes. The distribution of heterozygosity number is well fit by a compound Poisson distribution. The N50 length of haplotype segments is 37.9 kb in our assembly, while the N50 scaffold length of the Ciona intestinalis assembly is 190 kb. We also infer diploid gene sequences from haplotype segments. According to our reconstruction, 85.4% of predicted gene sequences are continuously covered by single haplotype segments. Our results indicate 97% accuracy in haplotype estimation, based on a simulated data set. We conduct a comparative analysis with Ciona savignyi, and discover interesting patterns of conserved DNA elements in chordates.
附：
吉布斯取样法(Gibbs sampler, GS)
Best等提出了一种更为通用的分析群体数据的方法，它可应用于较广范围的复杂模型而同时却没有诸如NONMEM法中的某些限制。此法并不需要计算出确切的或近似的参数估定值，而是通过一种称为Gibbs sampling的计算法对所感兴趣的参数给出一系列模拟值，这些值可用来重新组成每一参数的概率，或进行适当简化以提供确切值或某个范围的数值。
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