Biology subjects

Kai Zhang

Publications and source records attributed to Kai Zhang.

4 recordsLinked to original sources

bioRxiv2016

Whole-genome sequencing of an advanced case of small-cell gallbladder neuroendocrine carcinoma

The majority of gallbladder cancer cases are discovered at later stages, which frequently leads to poor prognoses. Small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC) is a relatively rare histological type of gallbladder cancer, and its survival rate is exceptionally low because of its greater malignant potential. In addition, the genomic landscape of GB-SCNEC is rarely considered in treatment decisions. We performed whole-genome sequencing on an advanced case of GB-SCNEC. By analyzing the whole-genome sequencing data of the primary cancer tissue (76.29X coverage), lymphatic metastatic cancer tissue (73.92X coverage) and matched non-cancerous tissue (35.73X coverage), we identified approximately 900 high-quality somatic single nucleotide variants (SNVs), 109 of which were shared by both the primary and metastatic tumor tissues. Somatic non-synonymous coding variations with damaging impact in HMCN1 and CDH10 were observed in both the primary and metastatic tissue specimens. A pathway analysis of the genes mapped to the SNVs revealed gene enrichment associated with axon guidance, ERBB signaling, sulfur metabolism and calcium signaling. Furthermore, we identified 20 chromosomal rearrangements that included 11 deletions, 4 tandem duplications and 5 inversions that mapped to known genes. Two gene fusions, NCAM2-SGCZ and BTG3-CCDC40 were also discovered and validated by Sanger sequencing. Additionally, we identified genome-wide copy number variations and microsatellite instability. In this study, we identified novel biological markers of GB-SCNEC that may serve as valuable prognostic factors or indicators of treatment response in patients with GB-SCNEC with lymphatic metastasis.

Genetics↗

bioRxiv2016

Plant diversity accurately predicts insect diversity in two tropical landscapes

Plant diversity surely determines arthropod diversity, but only moderate correlations between arthropod and plant species richness had been observed until Basset et al. (2012, Science 338: 1481-1484) finally undertook an unprecedentedly comprehensive sampling of a tropical forest and demonstrated that plant species richness could indeed accurately predict arthropod species richness. We now require a high-throughput pipeline to operationalize this result so that we can (1) test competing explanations for tropical arthropod megadiversity, (2) improve estimates of global eukaryotic species diversity, and (3) use plant and arthropod communities as efficient proxies for each other, thus improving the efficiency of conservation planning and of detecting forest degradation and recovery. We therefore applied metabarcoding to Malaise-trap samples across two tropical landscapes in China. We demonstrate that plant species richness can accurately predict arthropod (mostly insect) species richness and that plant and insect community compositions are highly correlated, even in landscapes that are large, heterogeneous, and anthropogenically modified. Finally, we review how metabarcoding makes feasible highly replicated tests of the major competing explanations for tropical megadiversity.

Ecology↗

bioRxiv2016

Systematic identification of cooperation between DNA binding proteins in 3D space

Cooperation between DNA-binding proteins (DBPs) such as transcription factors and chromatin remodeling enzymes plays a pivotal role in regulating gene expression and other biological processes. Such cooperation is often via interaction between DBPs that bind to loci located distal in the linear genome but close in the 3D space, referred as trans-cooperation. Due to the lack of 3D chromosomal structure, identification of DBP cooperation has been limited to those binding to neighbor regions in the linear genome, referred as cis-cooperation. Here we present the first study that integrates protein ChIP-seq and Hi-C data to systematically identify both cis- and trans-cooperation between DBPs. We developed a new network model that allows identification of cooperation between multiple DBPs and reveals cell type specific or independent regulations. Particularly interesting, we have retrieved many known and previously unknown trans-cooperation between DBPs in the chromosomal loops that may be a key factor for influencing 3D chromosomal structure. The software is available at http://wanglab.ucsd.edu/star/DBPnet/index.html.

Bioinformatics↗

bioRxiv2015

Gctf: real-time CTF determination and correction

Accurate estimation of the contrast transfer function (CTF) is critical for a near-atomic resolution cryo electron microscopy (cryoEM) reconstruction. Here, I present a GPU-accelerated computer program, Gctf, for accurate and robust, real-time CTF determination. Similar to alternative programs, the main target of Gctf is to maximize the cross-correlation of a simulated CTF with the power spectra of observed micrographs after background reduction. However, novel approaches in Gctf improve both speed and accuracy. In addition to GPU acceleration, a fast 1-dimensional search plus 2-dimensional refinement (1S2R) procedure significantly speeds up Gctf. Based on the global CTF determination, the local defocus for each particle and for single frames of movies is accurately refined, which improves CTF parameters of all particles for subsequent image processing. Novel diagnosis method using equiphase averaging(EFA) and self-consistency verification procedures have also been implemented in the program for practical use, especially for aims of near-atomic reconstruction. Gctf is an independent program and the outputs can be easily imported into other cryoEM software such as Relion and Frealign. The results from several representative datasets are shown and discussed in this paper.

Biophysics↗