Structural analysis of missense mutations in galactokinase 1 (GALK1) leading to galactosemia type‐2

Galactosemia type 2 is an autosomal recessive disorder characterized by the deficiency of galactokinase (GALK) enzyme due to missense mutations in GALK1 gene, which is associated with various manifestations such as hyper galactosemia and formation of cataracts. GALK enzyme catalyzes the adenosine triphosphate (ATP)–dependent phosphorylation of α‐d ‐galactose to galactose‐1‐phosphate. We searched 4 different literature databases (Google Scholar, PubMed, PubMed Central, and Science Direct) and 3 gene‐variant databases (Online Mendelian Inheritance in Man, Human Gene Mutation Database, and UniProt) to collect all the reported missense mutations associated with GALK deficiency. Our search strategy yielded 32 missense mutations. We used several computational tools (pathogenicity and stability, biophysical characterization, and physiochemical analyses) to prioritize the most significant mutations for further analyses. On the basis of the pathogenicity and stability predictions, 3 mutations (P28T, A198V, and L139P) were chosen to be tested further for physicochemical characterization, molecular docking, and simulation analyses. Molecular docking analysis revealed a decrease in interaction between the protein and ATP in all the 3 mutations, and molecular dynamic simulations of 50 ns showed a loss of stability and compactness in the mutant proteins. As the next step, comparative physicochemical changes of the native and the mutant proteins were carried out using essential dynamics. Overall, P28T and A198V were predicted to alter the structure and function of GALK protein when compared to the mutant L139P. This study demonstrates the power of computational analysis in variant classification and interpretation and provides a platform for developing targeted therapeutics.     

Accurate haplotype imputation with individualized ancestry-adjusted reference panels

Accurate data imputation requires ethnicity-matched reference panels. However, recent admixtures have created mosaic human genomes, different chromosomal segments have different ethnic backgrounds, so it is impossible for a single-ethnicity reference panel to be the matched for data imputation. In this study, we explored a novel strategy for imputation. We created individualized mosaic reference panel for each person according to his/her ethnic backgrounds at each genomic locus. We examined on datasets with 70% missing values on haplotypes and 50% missing values on genotypes. Results showed that the imputation with mosaic references steadily yielded high imputation accuracy and outperforms the other strategies. With the mosaic reference panels, the imputation accuracy was 98.8 ± 0.1% (CEU), 98.7 ± 0.1% (YRI), 98.5 ± 0.1% (CHB), 98.6 ± 0.1% (ASW), 97.3 ± 0.1% (MKK) and 98.2 ± 0.1% (MXL). Mosaic reference panel will be one option for future missing value imputation in big data era.     

宏蛋白质组学信息分析的基本策略及其挑战

宏蛋白质组学是一门新型科学,它运用质谱技术规模化地采集自然界微生物种群的蛋白质信息,并结合多种组学数据,开展微生物种群的遗传特征及其生物功能的研究.宏蛋白质组学的信息分析与传统蛋白质组学方法有较大的不同,亟需拓展新的分析思路.由于宏蛋白质组的研究对象是复杂度极高的微生物样品,因此,需要构建尽可能囊括样本中所含微生物的基因组信息的物种数据库.面对庞大的数据库,必须考虑到分析过程中所消耗的计算资源和鉴定结果的质控标准,因此,需要高度优化库容量、搜库、假阳性控制等参数.鉴于宏蛋白质组数据中广泛存在复杂的同源蛋白质序列,因此,需要充分利用NCBI数据库中的分类信息进行匹配,并运用LCA算法过滤处理才能将蛋白质有效地归组到物种.本文立足于宏蛋白质组学信息分析,从宏蛋白质组的数据库建立、蛋白质归并、生物学意义发掘等几个方面着手,对该领域的发展现状、面临挑战以及未来研究方向进行了评述.     

Population parameters and reproduction of the piranha Serrasalmus marginatus in the Negro river,Pantanal, Brazil

This paper aimed to define the reproductive period and population parameters of Serrasalmus marginatus relative to local environmental features, such as day length, rainfall and mean river level. The study site was a floodplain in the Negro river, Pantanal, Brazil, and samples were collected bimonthly using gill nets and cast nets with meshes from 1.5 to 8 cm between adjacent knots. The reproduction period, as determined by gonadosomatic index (GSI) and percentage of gonad stages, varied significantly along the year (F_4,116 = 77.5; p < 0.01), but it was well defined from October to December. Reproduction period was positively correlated with rainfall (rs = 0.97; p < 0.01) and photoperiod (rs = 0.92; p = 0.02), but not with the rise of river level (rs = 0.10; p = 0.86). Rainfall and photoperiod may act as predictive factors, providing cues to fish to begin reproduction in order to find the best conditions for offspring in the following months, during the flooding season, when the river level reaches its peak and extends to the plain. We have herein reported the first population parameters described for this species in the Brazilian Pantanal, including growth rate (k = 0.53/year), asymptotic length (L∞ = 32.74), lifespan (A_0.95 = 5.65) and mortality (M = 1.11), showing that this population has better growth performance when compared to data reported for this same species in the Paraná river since the population in the Negro river is characterized by lower growth and mortality rates, and S. marginatus achieved longer lengths and lifespan. This latter parameter was compatible with six cohorts estimated by Electronic Length Frequency Analysis (ELEFAN). The size at first maturity (L50 = 18.26 cm A50 = 1.56 years) was also larger and later than the population in the Paraná river, likely a consequence of the the lower mortality and the maintenance of larger specimens in the Negro river.     

Mapping Causal Variants with Single-Nucleotide Resolution Reveals Biochemical Drivers of Phenotypic Change

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Oreocharis duyunensis (Gesneriaceae), a new species from Guizhou,China

Oreocharis duyunensis Z.Y. Li, X.G. Xiang et Z.Y. Guo (Gesneriaceae), endemic to Guizhou, China, is described as a new species. The new species is easily distinguished from other Oreocharis species by having a white, stellate ring‐like disc. Morphologically, the species is similar to Oreocharis chienii (Chun) Mich. Möller & A. Weber but differs by its densely white pilose leaves, mixed brown‐pilose, pubescent and glandular‐pubescent peduncle and pedicle, white stellate ring‐like disc, and linear‐lanceolate capsule. Based on phylogenetic reconstruction and interspecific genetic distances of nuclear ITS and chloroplast trnL‐F regions, O. duyunensis is a new species with uncertain phylogenetic position.     

The many faces of Peridinium cinctum (Peridiniaceae,Peridiniales): morphological and molecular variability in a common dinophyte

Peridinium cinctum is a common freshwater dinophyte with a long history of research. Erich Lindemann was the first to assess intraspecific variability in this species focusing on plate pattern variation. Since then, this issue has been neglected but with the application of DNA sequence diagnostics, a combination of morphological and molecular characters may enable taxonomic delimitations. Our aim was to identify distinct morphotypes using plate pattern as the main characteristic and then compare them to the geographic occurrence of particular ribotypes (as inferred from sequences of the Internal Transcribed Spacer: ITS) in samples from Central Europe. Approximately 200 observations were carried out under the inverse light microscope for each of a total of 15 strains. We observed two main variations from the abundant plate pattern in P. cinctum, namely an unusual position of the 2a plate and the irregular shape of the 1a plate. In 88 (predominantly clonal) strains, we identified five different ribotypes (submitted as 71 new GenBank entries) which had no clear correlation to the defined morphotypes and/or spatial occurrences. In four cases, we detected two distinct ribotypes at the same locality. However, samples collected south of the Danube River presented a different predominant morphotype from the rest of the samples, thus implying a potential biogeographic signal as inferred from morphology. In general, there is morphological and molecular variability in P. cinctum, which is under-studied and which may uncover geographic or ecological correlations or even the existence of cryptic species.     

ReadTools: A universal toolkit for handling sequence data from different sequencing platforms

Sequencing whole genomes has become a standard research tool in many disciplines including Molecular Ecology, but the rapid technological advances in combination with several competing platforms have resulted in a confusing diversity of formats. This lack of standard formats causes several problems, such as undocumented preprocessing steps or the loss of information in downstream software tools, which do not account for the specifics of the different available formats. ReadTools is an open‐source Java toolkit designed to standardize and preprocess read data from different platforms. It manages FASTQ‐ and SAM‐formatted inputs while dealing with platform‐specific peculiarities and provides a standard SAM compliant output. The code and executable are available at https://github.com/magicDGS/ReadTools .