Grading amino acid properties increased accuracies of single point mutation on protein stability prediction

Abstract Background Protein stabilities can be affected sometimes by point mutations introduced to the protein. Current sequence-information-based protein stability prediction encoding schemes of machine learning approaches include sparse encoding and amino acid property encoding. Property encoding schemes employ physical-chemical information of the mutated protein environments, however, they produce complexity in the mean time when many properties joined in the scheme. The complexity introduces noises that affect machine learning algorithm accuracies. In order to overcome the problem we described a new encoding scheme that graded twenty amino acids into groups according to their specific property values. Results We employed three predefined values, 0.1, 0.5, and 0.9 to represent 'weak', 'middle', and 'strong' groups for each amino acid property, and introduced two thresholds for each property to split twenty amino acids into one of the three groups according to their property values. Each amino acid can take only one out of three predefined values rather than twenty different values for each property. The complexity and noises in the encoding schemes were reduced in this way. More than 7% average accuracy improvement was found in the graded amino acid property encoding schemes by 20-fold cross validation. The overall accuracy of our method is more than 72% when performed on the independent test sets starting from sequence information with three-state prediction definitions. Conclusions Grading numeric values of amino acid property can reduce the noises and complexity of input information. It is in accordance with biochemical concepts for amino acid properties and makes the input data simplified in the mean time. The idea of graded property encoding schemes may be applied to protein related predictions with machine learning approaches.</p

Effects of Atrazine on the Development of Neural System of Zebrafish, Danio rerio

By comparative analysis of histomorphology and AChE activity, the changes of physiological and biochemical parameters were determined in zebrafish embryos and larvae dealt with atrazine (ATR) at different concentrations (0.0001, 0.001, 0.01, 0.1, and 1 mg/L). This study showed that the development of the sarcomere and the arrangement of white muscle myofibers were affected by ATR significantly and the length of sarcomere shortened. Further analysis of the results showed that the AChE activity in juvenile fish which was treated with ATR was downregulated, which can indicate that the innervation efficiency to the muscle was impaired. Conversely, the AChE activity in zebrafish embryos which was treated with ATR was upregulated. A parallel phenomenon showed that embryonic primary sensory neurons (Rohon-Beard cells), principally expressing AChE in embryos, survived the physiological apoptosis. These phenomena demonstrated that the motor integration ability of the zebrafish was damaged by ATR which can disturb the development of sensory neurons and sarcomere and the innervations of muscle

Rab2 and Rab6 are Implicated in Acrosome Formation during Spermatogenesis in Eriocheir sinensis: Based on Sperm Proteome

Background: Rab proteins are GTP-dependent small proteins that function as regulators of intracellular vesicle transport, fusion, and localization. However, few studies have investigated their function in Decapoda reproduction. The Eriocheir sinensis sperm has no tail and the nuclei are uncondensed. With the acrosome forming the majority of the sperm mass, it provides an ideal model for studying acrosome formation. Methods: We firstly analyzed the sperm proteome using LC-MS/MS. To study the functions of Rab2 and Rab6, related to the Golgi apparatus, in the acrosome formation during spermatogenesis, the genes of Rab2 and Rab6 were cloned based on the testis transcriptome of E.sinensis and poly-clonal antibodies were prepared. The presence of 2 Rab proteins was confirmed in the testis and sperm by western blot. We further observed the characteristics of target 2 Rab proteins using immunofluorescence (IF). Results: A total of 1247 proteins including 7 Rab proteins, Rab1, Rab2, Rab5, Rab6, Rab11, Rab14, and Rab18 were identified in the sperm proteome. The IF results showed that Rab2 co-localizes with GM130, a cis-Golgi matrix protein, in the spermatagonia and spermatocytes. In the early spermatids, Rab2 and Rab6 participate in the formation of pre-acrosomal vesicles. In maturing spermatids, both Rab2 and Rab6 settle on the acrosomal membrane but present different characteristics wrapping the pre-acrosome. In the mature sperm, Rab2 localizes in the perinuclear theca surrounding the nuclei cup, while Rab6 remains on the acrosomal membrane. Conclusions: Our research found 7 Rab proteins based on the analysis of the sperm proteome in E.sinensis, and confirmed the involvement of Rab2 and Rab6 in acrosome formation. These findings provide a foundation for studying the functions of Rab proteins during spermatogenesis in Decapoda animals

Transcriptome and proteome reveal abnormal spermatozoa in precocious Chinese mitten crab, Eriocheir sinensis

In juvenile Chinese mitten crabs, Eriocheir sinensis, the occurrence of sexual gland maturation in the first year is known as precocity and significantly affects culture productivity and profitability. The miniaturization of individuals is a key characteristic of precocious crabs. Most related studies focus on the underlying causes, nutritional quality, biochemical components and differentially expressed mRNAs of precocious crab individuals and tissues. The reproductive performance of precocious crabs is evaluated based on offspring quality. However, the status of precocious parental gametes (especially spermatozoa) directly related to the offspring has not been reported. To clarify the differences in spermatozoa between precocious and normal mature crabs, spermatozoal transcriptome and proteome data were obtained via high-throughput sequencing technology. The results revealed a total of 856 differentially expressed genes and 150 differentially expressed proteins in spermatozoa. Functional analysis showed that these genes and proteins identified in the spermatozoa of precocious E. sinensis were significantly enriched in the categories of substance and energy metabolism. And more, the miniaturization of spermatogenic cells was also identified in precocious crabs. This indicates that metabolic disorders might be the main reason for the miniaturization of spermatogenic cells in precocious E. sinensis males. The molecular defects in precocious sperm were closely related to the imbalances in essential substance and energy metabolism. These findings provide foundational information and insights into hidden biological irregularities associated with precocious phenotypes and will contribute to the further study of precocious E. sinensis males and even other crustaceans

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China

Information on subjects harbouring HIV-1 recombinant strains unknown before in Hebei, China.

<p>Information on subjects harbouring HIV-1 recombinant strains unknown before in Hebei, China.</p

Geographic distribution of HIV-1 genotypes in Hebei in 2013.

<p>This figure is adapted from open access map: <a href="http://map.ps123.net/ditu/HTML/8939.html" target="_blank">http://map.ps123.net/ditu/HTML/8939.html</a> with Microsoft PowerPoint 2016.</p

Genomic mosaic structure maps of 34 recombinant forms unknown before in Hebei.

<p>The jpHMM-HIV Program (<a href="http://jphmm.gobics.de/submission_hiv.html" target="_blank">http://jphmm.gobics.de/submission_hiv.html</a>) was used to generate the mosaic structure maps based on HXB2 numbering. The different coloured symbols represent different genotype gene fragments. N/A denotes the missing information due to uninformative genotype models. 13CZ026 (underlined) listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171481#pone.0171481.s003" target="_blank">S3 Fig</a> which was subtype C identified using jpHMM-HIV is not shown.</p

Demographic and geographic distribution of HIV-1 genotypes in Hebei.

<p>Demographic and geographic distribution of HIV-1 genotypes in Hebei.</p