Browsing by Author "Hung, Jui-Hung"

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A 135-mW Fully Integrated Data Processor for Next-Generation Sequencing
(2017-12-01)
Wu, Yi-Chung
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Chang, Chia-Hua
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Hung, Jui-Hung
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Yang, Chia-Hsiang
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分子醫學與生物工程研究所
Next-generation sequencing (NGS) enables high-throughput sequencing, in which short DNA fragments can be sequenced in a massively parallel fashion. However, the essential algorithm behind the succeeding NGS data analysis, DNA mapping, is still excessively time consuming. DNA mapping can be partitioned into two parts: suffix array (SA) sorting and backward searching. Dedicated hardware designs for the less-complex backward searching have been proposed, but feasible hardware for the most complicated part, SA sorting, has never been explored. Based on the memory-efficient sBWT algorithm, this work is the first integrated NGS data processor for the entire DNA mapping. The k-ordered Ferragina and Manzini index used in the sBWT algorithm is leveraged to improve storage capacity and reduce hardware complexity. The proposed NGS data processor realizes the sBWT algorithm through bucket sorting, suffix grouping, and suffix sorting circuits. Key design parameters are analyzed to achieve the optimal performance with respect to hardware cost and execution time. Fabricated in 40-nm CMOS, the NGS data processor dissipates 135 mW at 200 MHz from a 0.9-V supply. With 1-GB external memory, the chip can analyze human DNA within 10 min. This work achieves 43 065x and 8 971x [3208x and 402x] higher energy efficiency (throughput-to-area ratio) than the high-end CPU and GPU solutions, respectively.
A 135mW Fully Integrated Data Processor for Next-Generation Sequencing
(2017-01-01)
Wu, Yi-Chung
;
Hung, Jui-Hung
;
Yang, Chia-Hsiang
;
交大名義發表
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National Chiao Tung University
A computational approach for identifying microRNA-target interactions using high-throughput CLIP and PAR-CLIP sequencing
(2013-01-21)
Chou, Chih-Hung
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Lin, Feng-Mao
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Chou, Min-Te
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Hsu, Sheng-Da
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Chang, Tzu-Hao
Background: MicroRNAs (miRNAs) play a critical role in down-regulating gene expression. By coupling with Argonaute family proteins, miRNAs bind to target sites on mRNAs and employ translational repression. A large amount of miRNA-target interactions (MTIs) have been identified by the crosslinking and immunoprecipitation (CLIP) and the photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) along with the next-generation sequencing (NGS). PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions. This artificial error obviously reduces the mappability of reads. However, a specific tool to analyze CLIP and PAR-CLIP data that takes T to C conversion into account is still in need. Results: We herein propose the first CLIP and PAR-CLIP sequencing analysis platform specifically for miRNA target analysis, namely miRTarCLIP. From scratch, it automatically removes adaptor sequences from raw reads, filters low quality reads, reverts C to T, aligns reads to 3'UTRs, scans for read clusters, identifies high confidence miRNA target sites, and provides annotations from external databases. With multi-threading techniques and our novel C to T reversion procedure, miRTarCLIP greatly reduces the running time comparing to conventional approaches. In addition, miRTarCLIP serves with a web-based interface to provide better user experiences in browsing and searching targets of interested miRNAs. To demonstrate the superior functionality of miRTarCLIP, we applied miRTarCLIP to two public available CLIP and PAR-CLIP sequencing datasets. miRTarCLIP not only shows comparable results to that of other existing tools in a much faster speed, but also reveals interesting features among these putative target sites. Specifically, we used miRTarCLIP to disclose that T to C conversion within position 1-7 and that within position 8-14 of miRNA target sites are significantly different (p value = 0.02), and even more significant when focusing on sites targeted by top 102 highly expressed miRNAs only (p value = 0.01). These results comply with previous findings and further suggest that combining miRNA expression and PAR-CLIP data can improve accuracy of the miRNA target prediction. Conclusion: To sum up, we devised a systematic approach for mining miRNA-target sites from CLIP-seq and PAR-CLIP sequencing data, and integrated the workflow with a graphical web-based browser, which provides a user friendly interface and detailed annotations of MTIs. We also showed through real-life examples that miRTarCLIP is a powerful tool for understanding miRNAs. Our integrated tool can be accessed online freely at http://miRTarCLIP.mbc.nctu.edu.tw.
A systematic optimized comparison algorithm for LDPC decoder
(2008)
Hung, Jui-Hui
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Hung, Jui-Hung
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Chen, Sau-Gee
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電子工程學系及電子研究所
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Department of Electronics Engineering and Institute of Electronics
This paper proposes a novel systematic optimized comparison algorithm for LDPC codes with arbitrary code lengths. Based on the presented algorithm, we also design a corresponding decoder architecture which has a short comparison delay time of [log(2)(n-1)] and a very low comparator complexity of n x [log(2) (n - 1)], where n is the input number to CNU. Besides, the proposed design is general, systematic and flexible, which can be applied to arbitrary input number of a CNU. The designed CNU is favorable to the existing CNU designs which are non-systematically designed with either longer critical path delays or higher comparator counts than the proposed designs. The proposed design is particularly good for long code length cases, when it is impractical to do customized optimized designs by hand, due to high design complexity.
Ash2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency network
(2019-11-04)
Tsai, Ping-Hsing
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Chien, Yueh
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Wang, Mong-Lien
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Hsu, Chih-Hung
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Laurent, Benoit
Pluripotency and cell fates can be modulated through the regulation of super-enhancers; however, the underlying mechanisms are unclear. Here, we showed a novel mechanism in which Ash2l directly binds to super-enhancers of several stemness genes to regulate pluripotency and self-renewal in pluripotent stem cells. Ash2l recruits Oct4/Sox2/Nanog (OSN) to form Ash2l/OSN complex at the super-enhancers of Jarid2, Nanog, Sox2 and Oct4, and further drives enhancer activation, upregulation of stemness genes, and maintains the pluripotent circuitry. Ash2l knockdown abrogates the OSN recruitment to all super-enhancers and further hinders the enhancer activation. In addition, CRISPRi/dCas9-mediated blocking of Ash2l-binding motifs at these super-enhancers also prevents OSN recruitment and enhancer activation, validating that Ash2l directly binds to super-enhancers and initiates the pluripotency network. Transfection of Ash2l with W118A mutation to disrupt Ash2l-Oct4 interaction fails to rescue Ash2l-driven enhancer activation and pluripotent gene upregulation in Ash2l-depleted pluripotent stem cells. Together, our data demonstrated Ash2l formed an enhancer-bound Ash2l/OSN complex that can drive enhancer activation, govern pluripotency network and stemness circuitry.
CYCLIC COMPARISON METHOD FOR LOW-DENSITY PARITY-CHECK DECODER
(2008-09-11)
HUNG, Jui-Hui
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Hung, Jui-Hung
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Chen, Sau-Gee
The present invention discloses a cyclic comparison method for an LDPC decoder, which applies to the comparators used in an LDPC decoder. According to the cyclic comparison algorithm of the present invention, the nth element of the input k elements, wherein n=1, . . . , k, is sequentially removed by the corresponding comparator to obtain k first series. Next, pairs of two elements selected from the k elements are used to form k second series. The preceding step is repeated k×log2(k−1) times to obtain k completion series. Either of one first series and one completion series contains (k−1) elements. The first series are compared with the completion series to determine whether they are identical. If they are identical, the process stops. If they are not identical, the abovementioned step is repeated to obtain new completion series. The cyclic comparison method of the present invention needs only k×log2(k−1) comparisons to obtain completion series. Thus, the present invention can reduce the number of basic operations and can apply to any input number. Further, the present invention can be easily programmed and can achieve the optimal solution.
dbPTM: an information repository of protein post-translational modification
(2006-01-01)
Lee, Tzong-Yi
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Huang, Hsien-Da
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Hung, Jui-Hung
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Huang, Hsi-Yuan
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Yang, Yuh-Shyong
dbPTM is a database that compiles information on protein post-translational modifications (PTMs), such as the catalytic sites, solvent accessibility of amino acid residues, protein secondary and tertiary structures, protein domains and protein variations. The database includes all of the experimentally validated PTM sites from Swiss-Prot, PhosphoELM and O-GLYCBASE. Only a small fraction of SwissProt proteins are annotated with experimentally verified PTM. Although the Swiss-Prot provides rich information about the PTM, other structural properties and functional information of proteins are also essential for elucidating protein mechanisms. The dbPTM systematically identifies three major types of protein PTM (phosphorylation, glycosylation and sulfation) sites against Swiss-Prot proteins by refining our previously developed prediction tool, KinasePhos (http://kinasephos.mbc.nctu.edu.tw/). Solvent accessibility and secondary structure of residues are also computationally predicted and are mapped to the PTM sites. The resource is now freely available at http://dbPTM.mbc.nctu.edu.tw/.
Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity
(2018-10-12)
Yen, Ya-Ping
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Hsieh, Wen-Fu
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Tsai, Ya-Yin
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Lu, Ya-Lin
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Liau, Ee Shan
The mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e., Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By profiling cell types at each stage of embryonic stem cell-derived motor neurons (ESC similar to MNs) that recapitulate spinal cord development, we uncovered that lncRNAs expressed from the Dlk1-Dio3 locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, Meg3 and other Dlk1-Dio3 locus-derived lncRNAs facilitate Ezh2/Jarid2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. Our data thus illustrate that these lncRNAs in the Dlk1-Dio3 locus, particularly Meg3, play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating Hox genes.
Epigenetic Regulation of WNT3A Enhancer during Regeneration of Injured Cortical Neurons
(2020-03-01)
Chang, Chu-Yuan
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Hung, Jui-Hung
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Huang, Liang-Wei
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Li, Joye
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Fung, Ka Shing
Traumatic brain injury is known to reprogram the epigenome. Chromatin immunoprecipitation-sequencing of histone H3 lysine 27 acetylation (H3K27ac) and tri-methylation of histone H3 at lysine 4 (H3K4me3) marks was performed to address the transcriptional regulation of candidate regeneration-associated genes. In this study, we identify a novel enhancer region for induced WNT3A transcription during regeneration of injured cortical neurons. We further demonstrated an increased mono-methylation of histone H3 at lysine 4 (H3K4me1) modification at this enhancer concomitant with a topological interaction between sub-regions of this enhancer and with promoter of WNT3A gene. Together, this study reports a novel mechanism for WNT3A gene transcription and reveals a potential therapeutic intervention for neuronal regeneration.
Factorbook.org: a Wiki-based database for transcription factor-binding data generated by the ENCODE consortium
(2013-01-01)
Wang, Jie
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Zhuang, Jiali
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Iyer, Sowmya
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Lin, Xin-Ying
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Greven, Melissa C.
The Encyclopedia of DNA Elements (ENCODE) consortium aims to identify all functional elements in the human genome including transcripts, transcriptional regulatory regions, along with their chromatin states and DNA methylation patterns. The ENCODE project generates data utilizing a variety of techniques that can enrich for regulatory regions, such as chromatin immunoprecipitation (ChIP), micrococcal nuclease (MNase) digestion and DNase I digestion, followed by deeply sequencing the resulting DNA. As part of the ENCODE project, we have developed a Web-accessible repository accessible at http://factorbook.org. In Wiki format, factorbook is a transcription factor (TF)-centric repository of all ENCODE ChIP-seq datasets on TF-binding regions, as well as the rich analysis results of these data. In the first release, factorbook contains 457 ChIP-seq datasets on 119 TFs in a number of human cell lines, the average profiles of histone modifications and nucleosome positioning around the TF-binding regions, sequence motifs enriched in the regions and the distance and orientation preferences between motif sites.
High-Resolution Mapping of Chromatin Packaging in Mouse Embryonic Stem Cells and Sperm
(2014-07-01)
Carone, Benjamin R.
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Hung, Jui-Hung
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Hainer, Sarah J.
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Chou, Min-Te
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Carone, Dawn M.
Mammalian embryonic stem cells (ESCs) and sperm exhibit unusual chromatin packaging that plays important roles in cellular function. Here, we extend a recently developed technique, based on deep paired-end sequencing of lightly digested chromatin, to assess footprints of nucleosomes and other DNA-binding proteins genome-wide in murine ESCs and sperm. In ESCs, we recover well-characterized features of chromatin such as promoter nucleosome depletion and further identify widespread footprints of sequence-specific DNA-binding proteins such as CTCF, which we validate in knockdown studies. We document global differences in nuclease accessibility between ESCs and sperm, finding that the majority of histone retention in sperm preferentially occurs in large gene-poor genomic regions, with only a small subset of nucleosomes being retained over promoters of developmental regulators. Finally, we describe evidence that CTCF remains associated with the genome in mature sperm, where it could play a role in organizing the sperm genome.
High-Resolution Mapping of Chromatin Packaging in Mouse Embryonic Stem Cells and Sperm
(2014-07-01)
Carone, Benjamin R.
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Hung, Jui-Hung
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Hainer, Sarah J.
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Chou, Min-Te
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Carone, Dawn M.
Mammalian embryonic stem cells (ESCs) and sperm exhibit unusual chromatin packaging that plays important roles in cellular function. Here, we extend a recently developed technique, based on deep paired-end sequencing of lightly digested chromatin, to assess footprints of nucleosomes and other DNA-binding proteins genome-wide in murine ESCs and sperm. In ESCs, we recover well-characterized features of chromatin such as promoter nucleosome depletion and further identify widespread footprints of sequence-specific DNA-binding proteins such as CTCF, which we validate in knockdown studies. We document global differences in nuclease accessibility between ESCs and sperm, finding that the majority of histone retention in sperm preferentially occurs in large gene-poor genomic regions, with only a small subset of nucleosomes being retained over promoters of developmental regulators. Finally, we describe evidence that CTCF remains associated with the genome in mature sperm, where it could play a role in organizing the sperm genome.
Mir-17 similar to 92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN
(2015-05-26)
Tung, Ying-Tsen
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Lu, Ya-Lin
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Peng, Kuan-Chih
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Yen, Ya-Ping
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Chang, Mien
Motor neurons (MNs) are unique because they project their axons outside of the CNS to innervate the peripheral muscles. Limb-innervating lateral motor column MNs (LMC-MNs) travel substantially to innervate distal limb mesenchyme. How LMC-MNs fine-tune the balance between survival and apoptosis while wiring the sensorimotor circuit en route remains unclear. Here, we show that the mir-17 similar to 92 cluster is enriched in embryonic stem cell (ESC)derived LMC-MNs and that conditional mir-17 similar to 92 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-17 similar to 92 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-17 similar to 92 responsible for LMC-MN degeneration. Additionally, mir-17 similar to 92 directly targets components of E3 ubiquitin ligases, affecting PTEN subcellular localization through monoubiquitination. This miRNA-mediated regulation modulates both target expression and target subcellular localization, providing LMC-MNs with an intricate defensive mechanism that controls their survival.
PEAT: an intelligent and efficient paired-end sequencing adapter trimming algorithm
(2015-01-21)
Li, Yun-Lung
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Weng, Jui-Cheng
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Hsiao, Chiung-Chih
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Chou, Min-Te
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Tseng, Chin-Wen
Background: In modern paired-end sequencing protocols short DNA fragments lead to adapter-appended reads. Current paired-end adapter removal approaches trim adapter by scanning the fragment of adapter on the 3' end of the reads, which are not competent in some applications. Results: Here, we propose a fast and highly accurate adapter-trimming algorithm, PEAT, designed specifically for paired-end sequencing. PEAT requires no a priori adaptor sequence, which is convenient for large-scale meta-analyses. We assessed the performance of PEAT with many adapter trimmers in both simulated and real life paired-end sequencing libraries. The importance of adapter trimming was exemplified by the influence of the downstream analyses on RNA-seq, ChIP-seq and MNase-seq. Several useful guidelines of applying adapter trimmers with aligners were suggested. Conclusions: PEAT can be easily included in the routine paired-end sequencing pipeline. The executable binaries and the standalone C++ source code package of PEAT are freely available online.
ProKware: integrated software for presenting protein structural properties in protein tertiary structures
(2006-07-01)
Hung, Jui-Hung
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Huang, Hsien-Da
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Lee, Tzong-Yi
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生物科技學系
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生物資訊及系統生物研究所
Protein tertiary structure plays an essential role in deciphering protein functions, especially protein structural properties, including domains, active sites and post-translational modifications. These properties typically yield useful clues for understanding protein functions. This work presents an integrated software, named ProKware, that presents protein structural properties in protein tertiary structures, such as domains, functional sites, families, active sites, binding sites, post-translational modifications and domain-domain interaction. Using this web-based and Windows-based interface, users can manipulate and visualize three-dimensional protein structures, as well as the supported structural properties that are curated in the protein knowledge database. ProKware is an effective and convenient solution for investigating protein functions and structural relationships. This software can be accessed on the internet at http://ProKware.mbc.nctu.edu.tw/.
sBWT: memory efficient implementation of the hardware-acceleration-friendly Schindler transform for the fast biological sequence mapping
(2016-11-15)
Chang, Chia-Hua
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Chou, Min-Te
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Wu, Yi-Chung
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Hong, Ting-Wei
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Li, Yun-Lung
Motivation: The Full-text index in Minute space (FM-index) derived from the Burrows-Wheeler transform (BWT) is broadly used for fast string matching in large genomes or a huge set of sequencing reads. Several graphic processing unit (GPU) accelerated aligners based on the FM-index have been proposed recently; however, the construction of the index is still handled by central processing unit (CPU), only parallelized in data level (e.g. by performing block-wise suffix sorting in GPU), or not scalable for large genomes. Results: To fulfill the need for a more practical, hardware-parallelizable indexing and matching approach, we herein propose sBWT based on a BWT variant (i.e. Schindler transform) that can be built with highly simplified hardware-acceleration-friendly algorithms and still suffices accurate and fast string matching in repetitive references. In our tests, the implementation achieves significant speedups in indexing and searching compared with other BWT-based tools and can be applied to a variety of domains.
SET-CYCLIC COMPARISON METHOD FOR LOW-DENSITY PARITY-CHECK DECODER
(2008-10-02)
HUNG, Jui-Hui
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Hung, Jui-Hung
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Chen, Sau-Gee
The present invention discloses a set-cyclic comparison method for an LDPC (Low-Density Parity-Check) decoder, which applies to a CNU (Check Node Unit) or a VNU (Variable Node Unit). In the systematized method of the present invention, all the input elements are initialized to obtain a matrix. Based on the symmetry of the matrix and the similarity between the rows of the matrix are sequentially formed different sets respectively corresponding to the horizontally-continuous elements having the maximum iteration number in the horizontal and vertical directions, the symmetric non-continuous non-boundary elements, and the boundary elements plus the end-around neighboring elements in the same row. The present invention applies to any input number. Via the large intersection between the compared sets, the present invention can effectively reduce the number of comparison calculations and greatly promote the performance of an LDPC decoder.
Tailor: a computational framework for detecting non-templated tailing of small silencing RNAs
(2015-09-30)
Chou, Min-Te
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Han, Bo W.
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Hsiao, Chiung-Po
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Zamore, Phillip D.
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Weng, Zhiping
Small silencing RNAs, including microRNAs, endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), have been shown to play important roles in fine-tuning gene expression, defending virus and controlling transposons. Loss of small silencing RNAs or components in their pathways often leads to severe developmental defects, including lethality and sterility. Recently, non-templated addition of nucleotides to the 3' end, namely tailing, was found to associate with the processing and stability of small silencing RNAs. Next Generation Sequencing has made it possible to detect such modifications at nucleotide resolution in an unprecedented throughput. Unfortunately, detecting such events from millions of short reads confounded by sequencing errors and RNA editing is still a tricky problem. Here, we developed a computational framework, Tailor, driven by an efficient and accurate aligner specifically designed for capturing the tailing events directly from the alignments without extensive post-processing. The performance of Tailor was fully tested and compared favorably with other general-purpose aligners using both simulated and real datasets for tailing analysis. Moreover, to show the broad utility of Tailor, we used Tailor to reanalyze published datasets and revealed novel findings worth further experimental validation. The source code and the executable binaries are freely available at https://github.com/jhhung/Tailor.
Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila
(2015-07-16)
Reimao-Pinto, Madalena M.
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Ignatova, Valentina
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Burkard, Thomas R.
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Hung, Jui-Hung
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Manzenreither, Raphael A.
Uridylation of RNA species represents an emerging theme in post-transcriptional gene regulation. In the microRNA pathway, such modifications regulate small RNA biogenesis and stability in plants, worms, and mammals. Here, we report Tailor, an uridylyltransferase that is required for the majority of 3\' end modifications of microRNAs in Drosophila and predominantly targets precursor hairpins. Uridylation modulates the characteristic two-nucleotide 3\' overhang of microRNA hairpins, which regulates processing by Dicer-1 and destabilizes RNA hairpins. Tailor preferentially uridylates mirtron hairpins, thereby impeding the production of non-canonical microRNAs. Mirtron selectivity is explained by primary sequence specificity of Tailor, selecting substrates ending with a 3\' guanosine. In contrast to mirtrons, conserved Drosophila precursor microRNAs are significantly depleted in 3\' guanosine, thereby escaping regulatory uridylation. Our data support the hypothesis that evolutionary adaptation to Tailor-directed uridylation shapes the nucleotide composition of precursor microRNA 3\' ends. Hence, hairpin uridylation may serve as a barrier for the de novo creation of microRNAs in Drosophila.