Asia Pacific Bioinformatics Conference Research Articles

Editorial

This special section of IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB) is a collection of papers presented at the 18th Asia Pacific Bioinformatics Conference (APBC2020), which was a virtual conference held in Seoul, Korea, from August 18 to 20 in 2020.

Guest Editorial for the 17th Asia Pacific Bioinformatics Conference

The eight papers in this special section were presented at the 17th Asia Pacific Bioinformatics Conference (APBC), which was held in Wuhan, China, 14-16 January 2019.

Guest Editorial for the 16th Asia Pacific Bioinformatics Conference

The eight papers in this special section were presented at the 16th Asia Pacific Bioinformatics Conference APBC2018, which was held in Yokohama, Japan, 15-17 January 2018. The aim of this conference is to provide an international forum for researchers, professionals, and industrial practitioners to share their knowledge and ideas of how to surf the tidal wave of information in the area of bioinformatics and computational biology.

Guest Editorial for the 15th Asia Pacific Bioinformatics Conference

The eight papers in this special section were presented at the 15th Asia Pacific Bioinformatics Conference (APBC2017), which was held in Shenzhen, China, 17-19 January 2017.

Guest Editorial for the 14th Asia Pacific Bioinformatics Conference

The eight papers in this special section were presented at the 14th Asia Pacific Bioinformatics Conference (APBC2016), which was held in San Francisco, USA, 11-13 January 2016.

Guest Editorial for the 13th Asia Pacific Bioinformatics Conference.

Guest Editorial for the 13th Asia Pacific Bioinformatics Conference.

Guest Editorial: Advanced Algorithms of Bioinformatics

Advanced algorithms can help to identify functional relationships of genes in a biological process, discovery sequence, and structural similarities and provide insights into the regulatory mechanism in bioinformatics. In this special section, three papers in their significantly extended versions were selected from the papers presented at the Tenth Asia Pacific Bioinformatics Conference (APBC2012). These papers have shown great cooperation and conscientious consideration throughout the challenging bioinformatics experiments.

Erratum to: CoNVEX: copy number variation estimation in exome sequencing data using HMM

Our proposed method, to detect copy number variations in whole exome sequencing data [1] was published in BMC Bioinformatics as a special issue containing the proceedings of The Eleventh Asia Pacific Bioinformatics Conference (APBC 2013). After the publication, it was brought to our attention that name of our software has a conflict with another software developed by a project carried out at Wellcome Trust Sanger Institute (http://www.uk10k.org/assets/ashg_vijayarangakannan_etal_2012.pdf). We were not aware of this project when we first named our method as CoNVEX, in mid 2012. Therefore, we would like to thank Dr. P. Vijayarangakannan, one of the developers of the other method, for bringing this to our attention. We would like to mention that, although both software share the same name, they are different in terms of computational methods and types of exome sequencing data used. To avoid any confusion associated with the software name, we would no longer call our software as CoNVEX. Our software will be further developed with a new project name, Aberration Detection in Tumour Exome (ADTEx).

The Tenth Asia Pacific Bioinformatics Conference (APBC 2012)

The Asia Pacific Bioinformatics Conference (APBC) is a leading conference in the Bioinformatics community and has grown rapidly since its inception in 2003. The goal of the annual conference series is to enable high quality interaction on bioinformatics research. The past APBC conferences were held in: 1. APBC 2003 4-7 Feb 2003: Adelaide, Australia 2. APBC 2004 18-22 Jan 2004: Dunedin, New Zealand 3. APBC 2005 17-21 Jan 2005: Singapore 4. APBC 2006 13-16 Feb 2006: Taipei, Taiwan 5. APBC 2007 15-17 Jan 2007: Hong Kong 6. APBC 2008 14-17 Jan 2008: Kyoto, Japan 7. APBC 2009 13-16 Jan 2009: Beijing, China 8. APBC 2010 18-21 Jan 2010: Bangalore, India 9. APBC 2011 11-14 Jan 2011: Incheon, Korea The Tenth Asia Pacific Bioinformatics Conference (APBC 2012) was held in Melbourne, Australia. The conference spanning the dates of the 17th to the 19th of January brought together more than 50 researchers, professionals, industry leaders and students from all over the globe. The participants came from institutions in the following 16 countries and regions (in alphabetical order): Australia, Canada, China, Germany, India, Netherlands, Japan, Poland, Portugal, Singapore, South Korea, Taiwan, Thailand, UK, USA and Vietnam. The conference program included 3 keynote speakers (Profs. Jenny Graves, Terry Speed, Peer Bork), 3 invited speakers (Profs. Steven Jones, Narayanaswamy Srinivasan, Robin Gasser), 42 selected talks, 3 tutorial sessions and 30 posters. The titles of the keynote talks were: • Jenny Graves, Weird Animal Genomes and Sex • Peer Bork, in Biology: From functional associations of tiny molecules to entire species • Terry Speed, Removing Unwanted Variation from Gene Expression Data The tutorial topics for APBC 2012 included: Analysis of Gene Expression and Proteomic Profiles based on Biological Networks (Limsoon Wong), Introduction to NGS informatics (Andrew Lonie), and Protein Inference: Concepts, Algorithms, and Software Tools (Zengyou He and Weichuan Yu). The emphasis of APBC has been algorithmic development and innovation in Bioinformatics and this year that theme continued. Reflecting the ever-changing nature of Bioinformatics and its adaption to advances in technology, a strong emphasis was placed on post sequencing data mining. A wide range of topics in Bioinformatics were covered at the conference and were categorised as: • Genome Evolution • Regulatory Studies • Gene Network Modelling • Micro/RNA Modelling • Database and Data Models • Protein - Protein Interaction • Protein Structural Prediction • Algorithmic Optimisation and Evaluation • Knowledge Reconstruction • Knowledge Modelling • Protein Drug Applications • Protein Binding Studies • Prediction Applications In 2012, APBC received a substantial number of submissions from a diverse range of countries. Participants in the 2012 APBC came from every continent with the exception of Africa; however actual participants may represent geographies outside of their institutions. The APBC 2012 conference has received 129 submissions covering a wide range of topics in Bioinformatics. The conference's scope was wide in order to adapt itself quickly to this progressive research field. The broad composition of the expert program committee was well equipped to handle the diversity of topics under the banner of Bioinformatics and Computational Biology. Of the 129 submitted papers, each paper was sent to three Program Committee members to review (102 papers received three peer reviews) and with an acceptance rate of 32.5%. We wish to thank and acknowledge the Program Committee members and their contributions. The Program Committee members are: • Tatsuya Akutsu, Kyoto University, Japan • Masanori Arita, University of Tokyo, Japan • Joel Bader, Johns Hopkins University, USA • Vladimir Brusic, Dana-Farber Cancer Institute, USA • Kun-Mao Chao, National Taiwan University, Taiwan • Yi-Ping Phoebe Chen, La Trobe University, Australia • Jake Yue Chen, Indiana U. School of Informatics, USA • Francis Chin, The University of Hong Kong, Hong Kong • Jung Kyoon Choi, KAIST, Korea • In-Sun Chu, KRIBB, Korea • Kyungsook Han, INHA University, Korea • Wen-Lian Hsu, Academia Sinica, Taiwan • Hsien-Da Huang, National Chiao Tung University, Taiwan • Daniel Huson, University at Tubingen, Tubingen • Jenn-Kang Hwang, National Chiao Tung University, Taiwan • Ju Han Kim, Seoul National University, Korea • Young Kim, KRIBB, Korea • Hyunju Lee, GIST, Korea • Sang Yup Lee, KAIST, Korea • Wentian Li, Feinstein Institute for Medical Research, USA • Jingchu Luo, Peking University, China • Bin Ma, University of Waterloo, Canada • Hiroshi Mamitsuka, Kyoto University, Japan • Geoff McLachlan, University of Queensland, Australia • Satoru Miyano, University of Tokyo, Japan • Shinichi Morishita, University of Tokyo, Japan • Kenta Nakai, University of Tokyo, Japan • Mark Ragan, University of Queensland, Australia • Naren Ramakrishan, Graduate Studies (bio), India • Cenk Sahinalp, SFU, Canada • Yasubumi Sakakibara, Keio University, Japan • David Sankoff, University of Ottawa, Canada • Thomas Schlitt, King's College London, United Kingdom • Ramanathan Sowdhamini, NCBS, India • Narayanaswamy Srinivasan, IISc, India • Wing-Kin Sung, National University of Singapore, Singapore • Alfonso Valencia, Centro Nacional de Biotechnologia, Spain • Lusheng Wang, The City University of Hong Kong, Hong Kong • Hong Yan, The City University of Hong Kong, Hong Kong • Ueng Cheng Yang, National Yang Ming University, Taiwan • S.M. Yiu, The University of Hong Kong, Hong Kong • Louxin Zhang, National University of Singapore, Singapore • Xuegong Zhang, Tsinghua University, China • Hongyu Zhao, Yale School of Public Health, USA • Jun Huan, University of Kansas, USA We would also like to thank all local Organizing Committee members behind the scenes, especially Phoebe Chen, Scott Mann, Howard Lee, Subha Kalyaanamoorthy, for their hard work on the website, local arrangement and many other miscellaneous tasks. We also thank Publication & Web Chair Scott Mann, Ka Ho Chi and Howard Lee.

The Ninth Asia Pacific Bioinformatics Conference (APBC2011)

The Asia Pacific Bioinformatics Conference (APBC) is a leading conference in the Bioinformatics community and has grown rapidly since its inception in 2003. The goal of the annual conference series is to enable high quality interaction on bioinformatics research. The past APBC conferences were held in: 1. APBC2003 4-7 Feb 2003: Adelaide Australia 2. APBC2004 18-22 Jan 2004: Dunedin, New Zealand 3. APBC2005 17-21 Jan 2005: Singapore 4. APBC2006 13-16 Feb, 2006: Taipei Taiwan 5. APBC2007 15-17 Jan, 2007: Hong Kong 6. APBC2008 14-17 Jan, 2008: Kyoto Japan 7. APBC2009 13-16 Jan, 2009: Beijing China 8. APBC2010 18-21 Jan, 2010: Bangalore India The Ninth Asia Pacific Bioinformatics Conference (APBC2011) was held in Incheon, South Korea, the first time in this dynamic country. The conference spanning the dates of the 11 to the 14 of January brought together more than 300 researchers, professional, industry leaders and students from all over the globe. The participants came from institutions in the following 19 countries and regions (in alphabetical order): Australia, Bangladesh, Belgium, Brazil, Canada, China, Germany, India, Italy, Poland, Portugal, Saudi Arabia, Singapore, South Korea, Switzerland, Taiwan, Thailand, UK and USA. The conference program included 6 keynote speakers (Drs. Steven Jones, Luonan Chen, Peer Bork, Sang Yup Lee, Hong Gil Nam and Kenta Nakai), 55 selected talks, 8 tutorials and more than 118 posters. The titles of the keynote talks are: • Steven Jones, “Bioinformatics and Cancer Genomics” • Luonan Chen, “Modeling and Analyzing Nonlinear Biomolecular Networks” • Peer Bork, “Systemic analysis of the human gut: connecting chemicals, proteins, cells, communities and phenotypes” • Sang Yup Lee, “Systems metabolic engineering” • Hong Gil Nam, “Understanding and controlling plant growth and development: Genetic, Systems, and chemical genomic approaches” • Kenta Nakai, “Information for Transcriptional Regulation” The tutorial topics for APBC2011 included WebLab: a web-based bioinformatics platform (Jingchu Luo), Promenade through the web programming for biological research using Perl language (Kyung-Hoon Kwon), Bioinformatics analysis of genome & exome by next generation sequencing (Namshim Kim), Probabilistic Models for Multiple Motif Discovery (Jong Kyoung), Molecular Modeling: Analysis of Protein Structure and Function (Jinhyuk Lee), OASIS: Traditional Korean Medicine Information Portal (Sang-Jun Yea), Information Retrieval and Text Mining Opportunities in Bioinformatics (Jeyakumar Natarajan) and Bioworks: Bioinformation Analysis Pipeline (Seungyoon Nam and Youngmahn Hahn). The emphasis of APBC has been algorithmic development and innovation in Bioinformatics and this year that theme continued. Reflecting the ever-changing nature of Bioinformatics and is adaption to advances in technology, for the first time, a session was held on next-generation sequencing. A wide range of topics in Bioinformatics were covered at the conference and were categorised as: • Phylogenetics and Evolution • Molecular binding and modelling • Genome Sequencing and Assembly • Network and system biology • Structural Bioinformatics • Pathway analysis • Proteomics * Correspondence: Phoebe.Chen@latrobe.edu.au La Trobe University, Melbourne, Australia Full list of author information is available at the end of the article Chen and Cho BMC Bioinformatics 2011, 12(Suppl 1):I1 http://www.biomedcentral.com/1471-2105/12/S1/I1

APBC 2010. The Eighth Asia Pacific Bioinformatics Conference Bangalore, India, 18-21 January 2010

The first Asia Pacific Bioinformatics Conference was held in 2003 in Adelaide, Australia, and has been an annual event ever since. While the locations of the previous conferences have been in the Pacific Rim, this is the first time that APBC is being held in South Asia. India is not just an emerging economy but also a burgeoning center for biotechnology and related sciences. This ISCB affiliated event was well publicized through the web, various related mailing lists and carefully targeted poster displays. We received a healthy number of submissions from 31 countries: Netherlands, Denmark, Chile, Sweden, Poland, Saudi Arabia, Portugal, Philippines, Malaysia, France, Ireland, Iran, New Zealand, United Arab Emirates, Norway, Israel, United Kingdom, Italy, Switzerland, Australia, Singapore, Japan, Republic of Korea, Germany, Bangladesh, Canada, Hong Kong, Taiwan, China, United States and India. We are happy to observe that the participation covers all continents, with the exception of Africa. While the list here has been compiled using the location of the affiliated institutes, we are certain that the authors themselves represent a wider geography than this. We received 231 submissions, about forty percent more than we expected (and surpassing each of the numbers in the previous editions of APBC). We have deliberately used a very flexible definition of bioinformatics, as it is a continually evolving field, to define the scope of the conference. The diverse composition of the program committee (see Additional file 1) was well equipped to handle the challenge of the broad spectrum of topics covered under the large, versatile umbrella of bioinformatics and computational biology. This is reflected in the following categorization of the subject matter: (1) Patterns and Motifs, (2) Gene Regulation, (3) Interactomics, (4) Functional Genomics, (5) Genomics & Metagenomics, (6) Proteomics, (7) Disease Studies, (8) Association Studies, (9) Comparative Genomics, (10) Structural Genomics and (11) Phylogeny. The program committee, working in all time-zones, did an excellent job, burning the midnight oil when required. We targeted about three independent reviews for each of the submissions. We received four reviews for 1 paper, two reviews for 49 papers and three reviews for each of the remaining. None of the papers with two reviews were close-calls. At the end of the day, we made the difficult decision of selecting 67 papers for oral presentation at the conference and publication in BMC Bioinformatics. We are cognizant of the fact that due to the typical constraints of a conference setting many worthy submissions did not make it to this short list. Judging by the diversity of the topics as well as the reviews, we have decided deliberately not to indulge in 'best paper' assignments. We are very grateful to the program committee members who invested a significant amount of time and energy, in spite of their busy schedules, to carry out their tasks in an objective and timely manner.

Going weighted: Parameterized algorithms for cluster editing

The goal of the Cluster Editing problem is to make the fewest changes to the edge set of an input graph such that the resulting graph is a disjoint union of cliques. This problem is NP-complete but recently, several parameterized algorithms have been proposed. In this paper, we present a number of surprisingly simple search tree algorithms for Weighted Cluster Editing assuming that edge insertion and deletion costs are positive integers. We show that the smallest search tree has size O ( 1.8 2 k ) for edit cost k , resulting in the currently fastest parameterized algorithm, both for this problem and its unweighted counterpart. We have implemented and compared our algorithms, and achieved promising results. 1 1 This is an extended version of two articles published in: Proc. of the 6th Asia Pacific Bioinformatics Conference, APBC 2008, in: Series on Advances in Bioinformatics and Computational Biology, vol. 5, Imperial College Press, pp. 211–220; and in: Proc. of the 2nd Conference on Combinatorial Optimization and Applications, COCOA 2008, in: LNCS, vol. 5038, Springer, pp. 289–302.

The Seventh Asia Pacific Bioinformatics Conference (APBC2009)

The Asia Pacific Bioinformatics Conference (APBC) series, founded in 2003, is an annual international forum for exploring research, development and applications of Bioinformatics and Computational Biology. The Seventh Asia Pacific Bioinformatics Conference (APBC2009) was held at Tsinghua University, Beijing, China during January 13–16 in 2009. It brought together more than 300 researchers, professionals, industrial practitioners and students from all over the world for interaction and exchange of knowledge and ideas in broad areas of bioinformatics and computational biology. The participants came from 21 nations and regions including (in alphabetical order) Australia, Belgium, Canada, China (the Mainland, Hong Kong and Taiwan), Denmark, Finland, France, Germany, Greece, India, Japan, Korea, the Netherlands, Poland, Singapore, Switzerland, Thailand, the United Kingdom, the USA and Vietnam. This represents the largest submission and participation in the history of APBC. The conference program includes 2 keynotes (Drs. David J. Lipman and Michael S. Waterman), 5 invited talks (Drs. Michael B. Eisen, Bailin Hao, John Mattick, Pavel Pevzner and Martin Vingron), 76 selected talks, 4 tutorial sessions and 120 posters. The titles of the keynote and invited talks are: • David J. Lipman: Molecular evolution and epidemiology of seasonal influenza • Michael S. Waterman: Sequence analysis using Eulerian graphs • Michael B. Eisen: Understanding and exploiting the evolution of Drosophila regulatory sequences • Bailin Hao: Independent verification of 16S rRNA based prokaryotic phylogeny by composition vector approach • John Mattick: A new understanding of the human genome • Pavel Pevzner: Genome Rearrangements: from Biological Problems to Combinatorial Algorithms • Martin Vingron: Transcriptional regulation: computational methods, statistics, and coregulation The topics of the four tutorials are: A structured approach for the dynamics modeling of biomolecular networks (David R. Gilbert, Robin Donaldson, Monika Heiner & Rainer Breitling), Natural language processing for biology: BioNLP (Zhiyong Lu & Kevin Cohen), Bayesian methods in genetic association studies (Matthew Stephens), and Systems biology based on integrated analysis of functional genomics data (Olga G. Troyanskaya). The APBC series had a tradition of emphasis on rigorous algorithm topics in bioinformatics and computation. In this year's conference, this hallmark was retained while the biological contexts of the topics were given more emphasis. Authors from more diverse backgrounds of computer science, biology, statistics, electrical engineering, medical sciences, chemistry and physics contributed to the conference. The selected papers and posters cover a wide range of themes in current bioinformatics and computational biology. The biological questions studied can be categorized into the following major fields: • DNA sequence analysis, alignment, evolution and comparative genomics, sequence assembly especially in the context of second-generation deep sequencing technology. • Gene regulation and expression analysis, including microarray data analysis and integration, transcriptional regulation, alternative splicing, and epigenomic factors. • RNA structure and function, especially non-coding RNAs including microRNAs and RNAi. • Proteins and proteomics, including protein structure, subcellular location and function and mass spectrometry data processing. • Biological pathways, networks and systems biology. • Disease and medical application study, genome-wide association studies. A total of 204 submissions were received and reviewed by a strong 63-member international Program Committee so that each submission is reviewed at least by 2 PC members, and more than 30 additional reviewers were invited by the PC members to provide extra reviews. The selected talks (all but one are collected in this supplement to BMC Bioinformatics) represent a 37% acceptance rate, and the authors have carefully revised the papers according to the reviews before the publication. A full proceedings of APBC2009, including all the accepted full papers and abstracts, is published by Tsinghua University Press. In conclusion we express our deep appreciation to the PC members and the additional reviewers who worked on a very tight schedule, sharing their valuable time and exquisite expertise in support of the review process. The PC members are: • Tatsuya Akutsu, Kyoto University • Joel Bader, Johns Hopkins University • Harmen Bussemaker, Columbia University • Andrea Califano, Columbia University • Francis Y.L. Chin, Hong Kong University, Hong Kong • Phoebe Chen, Deakin University • Runsheng Chen, Institute of Biophysics, CAS • Xue-wen Chen, University of Kansas • Nadia El-Mabrouk, University of Montreal • Mikhail Gelfand, Russian Academy of Science • Roderic Guigo, Centre de Regulacio Genomica, Barcelona • Jing-Dong Jackie Han, CA • Jenn-Kang Hwang, National Chiao Tung University • Sridhar Hannenhalli, University of Pennsylvania • Daniel Huson, University of Tubingen • Rui Jiang, Tsinghua University • Tao Jiang, University of California Riverside • Samuel Kaski, Helsinki University of Technology • Uri Keich, Cornell University • Luhua Lai, Peking University • Tak Wah Lam, University of Hong Kong • Charles Lawrence, Brown University • Chris Lee, UCLA • Doheon Lee, KAIST • Sang Yup Lee, KAIST • Cheng Li, DFCI/HSPH • Hao Li, UCSF • Jinyan Li, Nanyang Technological University • Wen-Hsiung Li, University of Chicago • Wentian Li, Feinstein Institute for Medical Research • Yixue Li, CAS and Shanghai Jiaotong University • Jun S. Liu, Harvard University • Jingchu Luo, Peking University • Bin Ma, University of Western Ontario • Hiroshi Mamitsuka, Kyoto University • Satoru Miyano, University of Tokyo • Kenta Nakai, University of Tokyo • Jurg Ott, Beijing Institute of Genomics, CAS • Laxmi Parida, IBM Watson Research Center • John Quackenbush, Harvard School of Public Health • Nikolaus Rajewsky, MDC-Berlin • Ron Shamir, Tel Aviv University • Steven Skiena, State University of New York at Stony Brook • Yun S. Song, University of California at Berkeley • Paul Spellman, Lawrence Berkeley National Laboratory • Fengzhu Sun, University of Southern California • Zhirong Sun, Tsinghua University • Masaru Tomita, Keio University • Martin Vingron, Max Planck Institute for Molecular Genetics • Lusheng Wang, City University of Hong Kong • Michael S. Waterman, University of Southern California • Limsoon Wong, National University of Singapore • Wing H. Wong, Stanford University • Eric Xing, Carnegie Mellon University • Ying Xu, University of Georgia, USA • Hong Xue, Hong Kong University of Science and Technology • Hong Yan, City University of Hong Kong • Weichuan Yu, Hong Kong University of Science and Technology • Luoxin Zhang, National University of Singapore • Michael Q. Zhang, Cold Spring Harbor Laboratory • Xuegong Zhang, Tsinghua University • Hongyu Zhao, Yale University • Qing Zhou, University of California at Los Angeles We would also like to thank all local Organizing Committee members for their hard work behind the scenes, especially the Poster Co-chairs Shao Li and Xiaoyan Zhu. We also wish to thank Eric P. Xing and Rui Jiang for organizing the excellent Tutorial session. We thank the conference secretaries Victor Renault, Xi Ma, Haiyan Luo, Tingting Li, Shicai Fan and Wendian Yan for their hard work on the website, technical editing, registration and many other miscellaneous tasks. We thank Tao Jiang, Phoebe Chen, Limsoon Wong and Jingchu Luo for their help and numerous suggestions. And we thank the National Natural Science Foundation of China (NSFC), the National Basic Research Program of China, the National Hi-tech Research and Development Program of China and Tsinghua University for their support.

The EAR-motif of the Cys2/His2-type Zinc Finger Protein Zat7 Plays a Key Role in the Defense Response of Arabidopsis to Salinity Stress

Cys2/His2-type zinc finger proteins, which contain the EAR transcriptional repressor domain, are thought to play a key role in regulating the defense response of plants to biotic and abiotic stress conditions. Although constitutive expression of several of these proteins was shown to enhance the tolerance of transgenic plants to abiotic stress, it is not clear whether the EAR-motif of these proteins is involved in this function. In addition, it is not clear whether suppression of plant growth, induced in transgenic plants by different Cys2/His2 EAR-containing proteins, is mediated by the EAR-domain. Here we report that transgenic Arabidopsis plants constitutively expressing the Cys2/His2 zinc finger protein Zat7 have suppressed growth and are more tolerant to salinity stress. A deletion or a mutation of the EAR-motif of Zat7 abolishes salinity tolerance without affecting growth suppression. These results demonstrate that the EAR-motif of Zat7 is directly involved in enhancing the tolerance of transgenic plants to salinity stress. In contrast, the EAR-motif appears not to be involved in suppressing the growth of transgenic plants. Further analysis of Zat7 using RNAi lines suggests that Zat7 functions in Arabidopsis to suppress a repressor of defense responses. A yeast two-hybrid analysis identified putative interactors of Zat7 and the EAR-domain, including WRKY70 and HASTY, a protein involved in miRNA transport. Our findings demonstrate that the EAR-domain of Cys2/His2-type zinc finger proteins plays a key role in the defense response of Arabidopsis to abiotic stresses.

Combinatorial Pattern Discovery Approach for the Folding Trajectory Analysis of a β-Hairpin

The study of protein folding mechanisms continues to be one of the most challenging problems in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape versus various reaction coordinates, such as the fraction of native contacts, the radius of gyration, RMSD from the native structure, and so on. In this paper, we present a combinatorial pattern discovery approach toward understanding the global state changes during the folding process. This is a first step toward an unsupervised (and perhaps eventually automated) approach toward identification of global states. The approach is based on computing biclusters (or patterned clusters)—each cluster is a combination of various reaction coordinates, and its signature pattern facilitates the computation of the Z-score for the cluster. For this discovery process, we present an algorithm of time complexity c∈RO((N + nm) log n), where N is the size of the output patterns and (n × m) is the size of the input with n time frames and m reaction coordinates. To date, this is the best time complexity for this problem. We next apply this to a β-hairpin folding trajectory and demonstrate that this approach extracts crucial information about protein folding intermediate states and mechanism. We make three observations about the approach: (1) The method recovers states previously obtained by visually analyzing free energy surfaces. (2) It also succeeds in extracting meaningful patterns and structures that had been overlooked in previous works, which provides a better understanding of the folding mechanism of the β-hairpin. These new patterns also interconnect various states in existing free energy surfaces versus different reaction coordinates. (3) The approach does not require calculating the free energy values, yet it offers an analysis comparable to, and sometimes better than, the methods that use free energy landscapes, thus validating the choice of reaction coordinates. (An abstract version of this work was presented at the 2005 Asia Pacific Bioinformatics Conference [1].)