Zhewen Zhang

A Brief Review of Software Tools for Pangenomics

Since the proposal for pangenomic study, there have been a dozen software tools actively in use for pangenomic analysis. By the end of 2014, Panseq and the pan-genomes analysis pipeline (PGAP) ranked as the top two most popular packages according to cumulative citations of peer-reviewed scientific publications. The functions of the software packages and tools, albeit variable among them, include categorizing orthologous genes, calculating pangenomic profiles, integrating gene annotations, and constructing phylogenies. As epigenomic elements are being gradually revealed in prokaryotes, it is expected that pangenomic databases and toolkits have to be extended to handle information of detailed functional annotations for genes and non-protein-coding sequences including non-coding RNAs, insertion elements, and conserved structural elements. To develop better bioinformatic tools, user feedback and integration of novel features are both of essence.

Transcriptome Analysis and Identification of Genes Related to Immune Function in Skin of the Chinese Brown Frog

The Chinese brown frog (Rana chensinensis) is a special amphibian in northern China, as it has been used widely in traditional Chinese medicine. The skin of the Chinese brown frog is also a promising resource for producing diverse antimicrobial peptides. To obtain a more comprehensive view of the metabolism and effective pharmacological components of Chinese brown frog skin, we constructed a non-normalized cDNA library from the skin. By sequencing cDNA clones at the 5′ end, we obtained 5,976 high-quality EST sequences, which clustered into 512 contigs and 1379 singletons (in all 1,891 clusters). After BLAST searches of the protein and nucleic acid databases in GenBank, we found 46.7% of clusters to have significant similarity to known sequences; 28% matched Xenopus tropicalis ESTs and 29.1% matched Xenopus laevis ESTs. Gene annotation results indicated that genes related to secretion and defensive function, such as ubiquitin, lectin, and proteinase inhibitors, are highly expressed in the skin. Whey acidic-domain proteins are also highly abundant in the skin. Furthermore, both a &bgr;-defensin and a lysozyme are transcribed in the frog skin, providing antibacterial protection. Analyses of gene ontology and KEGG metabolic pathways indicated the physiological roles of Chinese brown frog skin.

Complete Genome Sequence of Acinetobacter baumannii ZW85-1

ABSTRACT Acinetobacter baumannii is an aerobic, nonmotile Gram-negative bacterium that causes nosocomial infections worldwide. Here, we report the complete genome sequence of Acinetobacter baumannii strain ZW85-1 and its two plasmids. One of the plasmids carries genes for NDM-1, which can hydrolyze a wide range of antibiotics.

Comparative Genomics Analysis of Streptomyces Species Reveals Their Adaptation to the Marine Environment and Their Diversity at the Genomic Level.

Over 200 genomes of streptomycete strains that were isolated from various environments are available from the NCBI. However, little is known about the characteristics that are linked to marine adaptation in marine-derived streptomycetes. The particularity and complexity of the marine environment suggest that marine streptomycetes are genetically diverse. Here, we sequenced nine strains from the Streptomyces genus that were isolated from different longitudes, latitudes, and depths of the South China Sea. Then we compared these strains to 22 NCBI downloaded streptomycete strains. Thirty-one streptomycete strains are clearly grouped into a marine-derived subgroup and multiple source subgroup-based phylogenetic tree. The phylogenetic analyses have revealed the dynamic process underlying streptomycete genome evolution, and lateral gene transfer is an important driving force during the process. Pan-genomics analyses have revealed that streptomycetes have an open pan-genome, which reflects the diversity of these streptomycetes and guarantees the species a quick and economical response to diverse environments. Functional and comparative genomics analyses indicate that the marine-derived streptomycetes subgroup possesses some common characteristics of marine adaptation. Our findings have expanded our knowledge of how ocean isolates of streptomycete strains adapt to marine environments. The availability of streptomycete genomes from the South China Sea will be beneficial for further analysis on marine streptomycetes and will enrich the South China Sea’s genetic data sources.

Genome Sequence Analysis of the Naphthenic Acid Degrading and Metal Resistant Bacterium Cupriavidus gilardii CR3

Cupriavidus sp. are generally heavy metal tolerant bacteria with the ability to degrade a variety of aromatic hydrocarbon compounds, although the degradation pathways and substrate versatilities remain largely unknown. Here we studied the bacterium Cupriavidus gilardii strain CR3, which was isolated from a natural asphalt deposit, and which was shown to utilize naphthenic acids as a sole carbon source. Genome sequencing of C. gilardii CR3 was carried out to elucidate possible mechanisms for the naphthenic acid biodegradation. The genome of C. gilardii CR3 was composed of two circular chromosomes chr1 and chr2 of respectively 3,539,530 bp and 2,039,213 bp in size. The genome for strain CR3 encoded 4,502 putative protein-coding genes, 59 tRNA genes, and many other non-coding genes. Many genes were associated with xenobiotic biodegradation and metal resistance functions. Pathway prediction for degradation of cyclohexanecarboxylic acid, a representative naphthenic acid, suggested that naphthenic acid undergoes initial ring-cleavage, after which the ring fission products can be degraded via several plausible degradation pathways including a mechanism similar to that used for fatty acid oxidation. The final metabolic products of these pathways are unstable or volatile compounds that were not toxic to CR3. Strain CR3 was also shown to have tolerance to at least 10 heavy metals, which was mainly achieved by self-detoxification through ion efflux, metal-complexation and metal-reduction, and a powerful DNA self-repair mechanism. Our genomic analysis suggests that CR3 is well adapted to survive the harsh environment in natural asphalts containing naphthenic acids and high concentrations of heavy metals.

Draft Genome Sequence of the Novel Agar-Digesting Marine Bacterium HQM9

Strain HQM9, an aerobic, rod-shaped marine bacterium from red algae, can produce agarases and liquefy solid plating media efficiently when agar is used as a coagulant. Here we report the draft genome sequence and the initial findings from a preliminary analysis of strain HQM9, which should be a novel species of Flavobacteriaceae.

Database Resources of the BIG Data Center in 2018

Abstract The BIG Data Center at Beijing Institute of Genomics (BIG) of the Chinese Academy of Sciences provides freely open access to a suite of database resources in support of worldwide research activities in both academia and industry. With the vast amounts of omics data generated at ever-greater scales and rates, the BIG Data Center is continually expanding, updating and enriching its core database resources through big-data integration and value-added curation, including BioCode (a repository archiving bioinformatics tool codes), BioProject (a biological project library), BioSample (a biological sample library), Genome Sequence Archive (GSA, a data repository for archiving raw sequence reads), Genome Warehouse (GWH, a centralized resource housing genome-scale data), Genome Variation Map (GVM, a public repository of genome variations), Gene Expression Nebulas (GEN, a database of gene expression profiles based on RNA-Seq data), Methylation Bank (MethBank, an integrated databank of DNA methylomes), and Science Wikis (a series of biological knowledge wikis for community annotations). In addition, three featured web services are provided, viz., BIG Search (search as a service; a scalable inter-domain text search engine), BIG SSO (single sign-on as a service; a user access control system to gain access to multiple independent systems with a single ID and password) and Gsub (submission as a service; a unified submission service for all relevant resources). All of these resources are publicly accessible through the home page of the BIG Data Center at http://bigd.big.ac.cn.

Synonymous codon usage analysis of hand, foot and mouth disease viruses: A comparative study on coxsackievirus A6, A10, A16, and enterovirus 71 from 2008 to 2015

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) have been considered major pathogens of hand, foot and mouth disease (HFMD) throughout the world for decades. In recent years, coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) have raised attention as two other serious pathogens of HFMD. The present study focused on the synonymous codon usage of four viruses isolated from 2008 to 2015, with particular attention on P1 (encoding capsid proteins) and P2-P3 regions (both encoding non-structural proteins) in the genomic RNA. Relative synonymous codon usage, effective number of codons, neutrality and correspondence were analyzed. The results indicated that these viruses prefer A/T at the third position in codons rather than G/C. The most frequent codons of 4 essential and 2 semi-essential amino acids, as well as a key amino acid of metabolic junctions (Glu) used in the four viruses are also the most frequently used in humans. Effective number of codons (ENC) values indicated weak codon usage bias in all the viruses. Relatively, the force of mutation pressure in the P1 region was found to be stronger than that in the P2-P3 region, and this force in the P1 region of CVA6 and EV71 was stronger than that of CVA10 and A16. The neutrality analysis results implied that mutation pressure plays a minor role in shaping codon bias of these viruses. Correspondence analysis indicated that the codon usage of EV71 strains varied much more than that of other viruses. In conclusion, the present study provides novel and comparative insight into the evolution of HFMD pathogens at the codon level.

NucMap: a database of genome-wide nucleosome positioning map across species

Abstract Dynamics of nucleosome positioning affects chromatin state, transcription and all other biological processes occurring on genomic DNA. While MNase-Seq has been used to depict nucleosome positioning map in eukaryote in the past years, nucleosome positioning data is increasing dramatically. To facilitate the usage of published data across studies, we developed a database named nucleosome positioning map (NucMap, http://bigd.big.ac.cn/nucmap). NucMap includes 798 experimental data from 477 samples across 15 species. With a series of functional modules, users can search profile of nucleosome positioning at the promoter region of each gene across all samples and make enrichment analysis on nucleosome positioning data in all genomic regions. Nucleosome browser was built to visualize the profiles of nucleosome positioning. Users can also visualize multiple sources of omics data with the nucleosome browser and make side-by-side comparisons. All processed data in the database are freely available. NucMap is the first comprehensive nucleosome positioning platform and it will serve as an important resource to facilitate the understanding of chromatin regulation.

PGAweb: A Web Server for Bacterial Pan-Genome Analysis

An astronomical increase in microbial genome data in recent years has led to strong demand for bioinformatic tools for pan-genome analysis within and across species. Here, we present PGAweb, a user-friendly, web-based tool for bacterial pan-genome analysis, which is composed of two main pan-genome analysis modules, PGAP and PGAP-X. PGAweb provides key interactive and customizable functions that include orthologous clustering, pan-genome profiling, sequence variation and evolution analysis, and functional classification. PGAweb presents features of genomic structural dynamics and sequence diversity with different visualization methods that are helpful for intuitively understanding the dynamics and evolution of bacterial genomes. PGAweb has an intuitive interface with one-click setting of parameters and is freely available at http://PGAweb.vlcc.cn/.