Jiayan Wu

PGAP: Pan-genomes analysis pipeline

Summary: With the rapid development of DNA sequencing technology, increasing bacteria genome data enable the biologists to dig the evolutionary and genetic information of prokaryotic species from pan-genome sight. Therefore, the high-efficiency pipelines for pan-genome analysis are mostly needed. We have developed a new pan-genome analysis pipeline (PGAP), which can perform five analytic functions with only one command, including cluster analysis of functional genes, pan-genome profile analysis, genetic variation analysis of functional genes, species evolution analysis and function enrichment analysis of gene clusters. PGAPs performance has been evaluated on 11 Streptococcus pyogenes strains. Availability:PGAP is developed with Perl script on the Linux Platform and the package is freely available from http://pgap.sf.net. Contact: junyu@big.ac.cn; xiaojingfa@big.ac.cn Supplementary information: Supplementary data are available at Bioinformatics online.

Genome sequence and genetic diversity of the common carp, Cyprinus carpio

The common carp, Cyprinus carpio, is one of the most important cyprinid species and globally accounts for 10% of freshwater aquaculture production. Here we present a draft genome of domesticated C. carpio (strain Songpu), whose current assembly contains 52,610 protein-coding genes and approximately 92.3% coverage of its paleotetraploidized genome (2n = 100). The latest round of whole-genome duplication has been estimated to have occurred approximately 8.2 million years ago. Genome resequencing of 33 representative individuals from worldwide populations demonstrates a single origin for C. carpio in 2 subspecies (C. carpio Haematopterus and C. carpio carpio). Integrative genomic and transcriptomic analyses were used to identify loci potentially associated with traits including scaling patterns and skin color. In combination with the high-resolution genetic map, the draft genome paves the way for better molecular studies and improved genome-assisted breeding of C. carpio and other closely related species.

Microrna cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition

MicroRNAs (miRNAs) are emerging critical regulators of cell function that frequently reside in clusters throughout the genome. They influence a myriad of cell functions, including the generation of induced pluripotent stem cells, also termed reprogramming. Here, we have successfully delivered entire miRNA clusters into reprogramming fibroblasts using retroviral vectors. This strategy avoids caveats associated with transient transfection of chemically synthesized miRNA mimics. Overexpression of 2 miRNA clusters, 106a–363 and in particular 302–367, allowed potent increases in induced pluripotent stem cell generation efficiency in mouse fibroblasts using 3 exogenous factors (Sox2, Klf4, and Oct4). Pathway analysis highlighted potential relevant effectors, including mesenchymal-to-epithelial transition, cell cycle, and epigenetic regulators. Further study showed that miRNA cluster 302–367 targeted TGFβ receptor 2, promoted increased E-cadherin expression, and accelerated mesenchymal-to-epithelial changes necessary for colony formation. Our work thus provides an interesting alternative for improving reprogramming using miRNAs and adds new evidence for the emerging relationship between pluripotency and the epithelial phenotype.

Generation of induced pluripotent stem cells from urine

Forced expression of selected transcription factors can transform somatic cells into embryonic stem cell (ESC)-like cells, termed induced pluripotent stem cells (iPSCs). There is no consensus regarding the preferred tissue from which to harvest donor cells for reprogramming into iPSCs, and some donor cell types may be more prone than others to accumulation of epigenetic imprints and somatic cell mutations. Here, we present a simple, reproducible, noninvasive method for generating human iPSCs from renal tubular cells present in urine. This procedure eliminates many problems associated with other protocols, and the resulting iPSCs display an excellent ability to differentiate. These data suggest that urine may be a preferred source for generating iPSCs.

Prepublication data sharing.

Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology.

ParaAT: a parallel tool for constructing multiple protein-coding DNA alignments.

Constructing multiple homologous alignments for protein-coding DNA sequences is crucial for a variety of bioinformatic analyses but remains computationally challenging. With the growing amount of sequence data available and the ongoing efforts largely dependent on protein-coding DNA alignments, there is an increasing demand for a tool that can process a large number of homologous groups and generate multiple protein-coding DNA alignments. Here we present a parallel tool - ParaAT that is capable of parallelly constructing multiple protein-coding DNA alignments for a large number of homologs. As testified on empirical datasets, ParaAT is well suited for large-scale data analysis in the high-throughput era, providing good scalability and exhibiting high parallel efficiency for computationally demanding tasks. ParaAT is freely available for academic use only at http://cbb.big.ac.cn/software.

Comparative genomic analysis of Streptococcus suis reveals significant genomic diversity among different serotypes

BackgroundStreptococcus suis (S. suis) is a major swine pathogen and an emerging zoonotic agent. Serotypes 1, 2, 3, 7, 9, 14 and 1/2 are the most prevalent serotypes of this pathogen. However, almost all studies were carried out on serotype 2 strains. Therefore, characterization of genomic features of other serotypes will be required to better understand their virulence potential and phylogenetic relationships among different serotypes.ResultsFour Chinese S. suis strains belonging to serotypes 1, 7, 9 and 1/2 were sequenced using a rapid, high-throughput approach. Based on the 13 corresponding serotype strains, including 9 previously completed genomes of this bacterium, a full comparative genomic analysis was performed. The results provide evidence that (i) the pan-genome of this species is open and the size increases with addition of new sequenced genomes, (ii) strains of serotypes 1, 3, 7 and 9 are phylogenetically distinct from serotype 2 strains, but all serotype 2 strains, plus the serotype 1/2 and 14 strains, are very closely related. (iii) all these strains, except for the serotype 1 strain, could harbor a recombinant site for a pathogenic island (89 K) mediated by conjugal transfer, and may have the ability to gain the 89 K sequence.ConclusionsThere is significant genomic diversity among different strains in S. suis, and the gain and loss of large amount of genes are involved in shaping their genomes. This is indicated by (i) pairwise gene content comparisons between every pair of these strains, (ii) the open pan-genome of this species, (iii) the observed indels, invertions and rearrangements in the collinearity analysis. Phylogenetic relationships may be associated with serotype, as serotype 2 strains are closely related and distinct from other serotypes like 1, 3, 7 and 9, but more strains need to be sequenced to confirm this.

Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes

Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation.

PanGP: A tool for quickly analyzing bacterial pan-genome profile

Summary: Pan-genome analyses have shed light on the dynamics and evolution of bacterial genome from the point of population. The explosive growth of bacterial genome sequence also brought an extremely big challenge to pan-genome profile analysis. We developed a tool, named PanGP, to complete pan-genome profile analysis for large-scale strains efficiently. PanGP has integrated two sampling algorithms, totally random (TR) and distance guide (DG). The DG algorithm drew sample strain combinations on the basis of genome diversity of bacterial population. The performance of these two algorithms have been evaluated on four bacteria populations with strain numbers varying from 30 to 200, and the DG algorithm exhibited overwhelming advantage on accuracy and stability than the TR algorithm. Availability: PanGP was developed with a user-friendly graphic interface and it was available at http://PanGP.big.ac.cn. Contact: xiaojingfa@big.ac.cn or wujy@big.ac.cn Supplementary information: Supplementary data are available at Bioinformatics online.