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Showing papers by "Wing-Kin Sung published in 2014"



Journal ArticleDOI
TL;DR: This is the first study that has provided an unprecedented transcriptomic-wide perspective of gill iono-osmoregulation and cellular remodeling in response to salinity challenge and acclimation.
Abstract: The Mozambique tilapia Oreochromis mossambicus has the ability to adapt to a broad range of environmental salinities and has long been used for investigating iono-osmoregulation. However, to date most studies have focused mainly on several key molecules or parameters hence yielding a limited perspective of the versatile iono-osmoregulation in the euryhaline fish. This study aimed to capture transcriptome-wide differences between the freshwater- and seawater-acclimated gills of the Mozambique tilapia. We have identified over 5000 annotated gene transcripts with high homology (E-value <1.0E-50) to human genes that were differentially expressed in freshwater- and seawater-acclimated gills of the Mozambique tilapia. These putative human homologs were found to be significantly associated with over 50 canonical signaling pathways that are operating in at least 23 biological processes in relation to branchial iono-osmoregulation and cellular remodeling. The analysis revealed multiple signaling pathways in freshwater-acclimated gills acting in concert to maintain cellular homeostasis under hypo-osmotic environment while seawater-acclimated gills abounded with molecular signals to cope with the higher cellular turn-over rate, energetics and iono-regulatory demands under hyper-osmostic stress. Additionally, over 100 transcripts encoding putative inorganic ion transporters/channels were identified, of which several are well established in gill iono-regulation while the remainder are lesser known. We have also validated the expression profiles of 47 representative genes in freshwater- and seawater-acclimated gills, as well as in hypersaline-acclimated (two-fold salinity of seawater) gills. The findings confirmed that many of these responsive genes retained their expression profiles in hypersaline-acclimated gills as in seawater-acclimated gills, although several genes had changed significantly in their expression level/direction in hypersaline-acclimated gills. This is the first study that has provided an unprecedented transcriptomic-wide perspective of gill iono-osmoregulation since such studies were initiated more than 80 years ago. It has expanded our molecular perspective from a relatively few well-studied molecules to a plethora of gene transcripts and a myriad of canonical signaling pathways driving various biological processes that are operating in gills under hypo-osmotic and hyper-osmotic stresses. These findings would provide insights and resources to fuel future studies on gill iono-osmoregulation and cellular remodeling in response to salinity challenge and acclimation.

65 citations


Journal ArticleDOI
TL;DR: This work describes a new data structure based on relative Lempel–Ziv compression that is space-efficient and also supports fast pattern searching.

57 citations


Journal ArticleDOI
11 Mar 2014-eLife
TL;DR: The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation of INPs back into type II neuroblasts, and the predicted Erm-binding motif is present in most of known binding loci of Brm.
Abstract: The control of self-renewal and differentiation of neural stem and progenitor cells is a crucial issue in stem cell and cancer biology. Drosophila type II neuroblast lineages are prone to developing impaired neuroblast homeostasis if the limited self-renewing potential of intermediate neural progenitors (INPs) is unrestrained. Here, we demonstrate that Drosophila SWI/SNF chromatin remodeling Brahma (Brm) complex functions cooperatively with another chromatin remodeling factor, Histone deacetylase 3 (HDAC3) to suppress the formation of ectopic type II neuroblasts. We show that multiple components of the Brm complex and HDAC3 physically associate with Earmuff (Erm), a type II-specific transcription factor that prevents dedifferentiation of INPs into neuroblasts. Consistently, the predicted Erm-binding motif is present in most of known binding loci of Brm. Furthermore, brm and hdac3 genetically interact with erm to prevent type II neuroblast overgrowth. Thus, the Brm-HDAC3-Erm repressor complex suppresses dedifferentiation of INPs back into type II neuroblasts. DOI: http://dx.doi.org/10.7554/eLife.01906.001

56 citations


Journal ArticleDOI
31 Mar 2014-Genomics
TL;DR: Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations in HCC.

45 citations


Journal ArticleDOI
04 Sep 2014-PLOS ONE
TL;DR: D5F3 immunohistochemistry, single-color CISH and IT-PGM sequencing are suitable assays for evaluation of ALK status in future neuroblastoma clinical trials, and correlation with ALK genomic and hotspot mutational status revealed that the majority of D5F2 ALK-positive cases did not possess either ALK genomes or hotspot mutations.
Abstract: ALK is an established causative oncogenic driver in neuroblastoma, and is likely to emerge as a routine biomarker in neuroblastoma diagnostics. At present, the optimal strategy for clinical diagnostic evaluation of ALK protein, genomic and hotspot mutation status is not well-studied. We evaluated ALK immunohistochemical (IHC) protein expression using three different antibodies (ALK1, 5A4 and D5F3 clones), ALK genomic status using single-color chromogenic in situ hybridization (CISH), and ALK hotspot mutation status using conventional Sanger sequencing and a next-generation sequencing platform (Ion Torrent Personal Genome Machine (IT-PGM)), in archival formalin-fixed, paraffin-embedded neuroblastoma samples. We found a significant difference in IHC results using the three different antibodies, with the highest percentage of positive cases seen on D5F3 immunohistochemistry. Correlation with ALK genomic and hotspot mutational status revealed that the majority of D5F3 ALK-positive cases did not possess either ALK genomic amplification or hotspot mutations. Comparison of sequencing platforms showed a perfect correlation between conventional Sanger and IT-PGM sequencing. Our findings suggest that D5F3 immunohistochemistry, single-color CISH and IT-PGM sequencing are suitable assays for evaluation of ALK status in future neuroblastoma clinical trials.

14 citations


Journal ArticleDOI
TL;DR: A new method to store density data named CWig is described, which uses on average one-third of the size of existing bigWig files and improves random query speed up to 100 times.
Abstract: Motivation BigWig, a format to represent read density data, is one of the most popular data types. They can represent the peak intensity in ChIP-seq, the transcript expression in RNA-seq, the copy number variation in whole genome sequencing, etc. UCSC Encode project uses the bigWig format heavily for storage and visualization. Of 5.2 TB Encode hg19 database, 1.6 TB (31% of the total space) is used to store bigWig files. BigWig format not only saves a lot of space but also supports fast queries that are crucial for interactive analysis and browsing. In our benchmark, bigWig often has similar size to the gzipped raw data, while is still able to support ∼ 5000 random queries per second. Results Although bigWig is good enough at the moment, both storage space and query time are expected to become limited when sequencing gets cheaper. This article describes a new method to store density data named CWig. The format uses on average one-third of the size of existing bigWig files and improves random query speed up to 100 times. Availability and implementation http://genome.ddns.comp.nus.edu.sg/∼cwig.

6 citations


Journal ArticleDOI
31 Jul 2014-PLOS ONE
TL;DR: It is shown that the SMRT does not seem to be an appropriate solution from the biological point of view, and a heuristic algorithm named MTRT is presented, which shows that triplets alone cannot provide enough information to infer the true MUL tree.
Abstract: The evolutionary history of certain species such as polyploids are modeled by a generalization of phylogenetic trees called multi-labeled phylogenetic trees, or MUL trees for short. One problem that relates to inferring a MUL tree is how to construct the smallest possible MUL tree that is consistent with a given set of rooted triplets, or SMRT problem for short. This problem is NP-hard. There is one algorithm for the SMRT problem which is exact and runs in time, where is the number of taxa. In this paper, we show that the SMRT does not seem to be an appropriate solution from the biological point of view. Indeed, we present a heuristic algorithm named MTRT for this problem and execute it on some real and simulated datasets. The results of MTRT show that triplets alone cannot provide enough information to infer the true MUL tree. So, it is inappropriate to infer a MUL tree using triplet information alone and considering the minimum number of duplications. Finally, we introduce some new problems which are more suitable from the biological point of view.

4 citations


Book ChapterDOI
15 Dec 2014
TL;DR: This paper shows how to compute the R* consensus tree of \(k\) rooted phylogenetic trees with \(n\) leaves each and identical leaf label sets in O(n^{2} \sqrt{\log n}) time.
Abstract: The fastest known algorithms for computing the R* consensus tree of \(k\) rooted phylogenetic trees with \(n\) leaves each and identical leaf label sets run in \(O(n^{2} \sqrt{\log n})\) time when \(k = 2\) (ref. [10]) and \(O(k n^{3})\) time when \(k \ge 3\) (ref. [4]). This paper shows how to compute it in \(O(n^{2})\) time for \(k = 2\), \(O(n^{2} \log ^{4/3} n)\) time for \(k = 3\), and \(O(n^{2} \log ^{k+2} n)\) time for unbounded \(k\).

2 citations


Journal ArticleDOI
TL;DR: The nine papers in this special section were presented at the 2013 International Conference on Genome Informatics, where the aim was to provide a platform for real-time decision-making on the structure and structure of the genome.
Abstract: The nine papers in this special section were presented at the 2013 International Conference on Genome Informatics.

1 citations