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Vladimir Brusic

Bio: Vladimir Brusic is an academic researcher from Nazarbayev University. The author has contributed to research in topics: Epitope & Human leukocyte antigen. The author has an hindex of 50, co-authored 212 publications receiving 13727 citations. Previous affiliations of Vladimir Brusic include Griffith University & Harvard University.


Papers
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Journal ArticleDOI
Piero Carninci, Takeya Kasukawa1, Shintaro Katayama, Julian Gough  +194 moreInstitutions (36)
02 Sep 2005-Science
TL;DR: Detailed polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
Abstract: This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

3,412 citations

Journal ArticleDOI
Yasushi Okazaki, Masaaki Furuno, Takeya Kasukawa1, Jun Adachi, Hidemasa Bono, S. Kondo, Itoshi Nikaido2, Naoki Osato, Rintaro Saito3, Harukazu Suzuki, Itaru Yamanaka, H. Kiyosawa2, Ken Yagi, Yasuhiro Tomaru4, Yuki Hasegawa2, A. Nogami2, Christian Schönbach, Takashi Gojobori, Richard M. Baldarelli, David P. Hill, Carol J. Bult, David A. Hume5, John Quackenbush6, Lynn M. Schriml7, Alexander Kanapin, Hideo Matsuda8, Serge Batalov9, Kirk W. Beisel10, Judith A. Blake, Dirck W. Bradt, Vladimir Brusic, Cyrus Chothia11, Lori E. Corbani, S. Cousins, Emiliano Dalla, Tommaso A. Dragani, Colin F. Fletcher9, Colin F. Fletcher12, Alistair R. R. Forrest5, K. S. Frazer13, Terry Gaasterland14, Manuela Gariboldi, Carmela Gissi15, Adam Godzik16, Julian Gough11, Sean M. Grimmond5, Stefano Gustincich17, Nobutaka Hirokawa18, Ian J. Jackson19, Erich D. Jarvis20, Akio Kanai3, Hideya Kawaji8, Hideya Kawaji1, Yuka Imamura Kawasawa21, Rafal M. Kedzierski21, Benjamin L. King, Akihiko Konagaya, Igor V. Kurochkin, Yong-Hwan Lee6, Boris Lenhard22, Paul A. Lyons23, Donna Maglott7, Lois J. Maltais, Luigi Marchionni, Louise M. McKenzie, Harukata Miki18, Takeshi Nagashima, Koji Numata3, Toshihisa Okido, William J. Pavan7, Geo Pertea6, Graziano Pesole15, Nikolai Petrovsky24, Ramesh S. Pillai, Joan Pontius7, D. Qi, Sridhar Ramachandran, Timothy Ravasi5, Jonathan C. Reed16, Deborah J Reed, Jeffrey G. Reid, Brian Z. Ring, M. Ringwald, Albin Sandelin22, Claudio Schneider, Colin A. Semple19, Mitsutoshi Setou18, K. Shimada25, Razvan Sultana6, Yoichi Takenaka8, Martin S. Taylor19, Rohan D. Teasdale5, Masaru Tomita3, Roberto Verardo, Lukas Wagner7, Claes Wahlestedt22, Y. Wang6, Yoshiki Watanabe25, Christine A. Wells5, Laurens G. Wilming26, Anthony Wynshaw-Boris27, Masashi Yanagisawa21, Ivana V. Yang6, L. Yang, Zheng Yuan5, Mihaela Zavolan14, Yunhui Zhu, Anne M. Zimmer28, Piero Carninci, N. Hayatsu, Tomoko Hirozane-Kishikawa, Hideaki Konno, M. Nakamura, Naoko Sakazume, K. Sato4, Toshiyuki Shiraki, Kazunori Waki, Jun Kawai, Katsunori Aizawa, Takahiro Arakawa, S. Fukuda, A. Hara, W. Hashizume, K. Imotani, Y. Ishii, Masayoshi Itoh, Ikuko Kagawa, A. Miyazaki, K. Sakai, D. Sasaki, K. Shibata, Akira Shinagawa, Ayako Yasunishi, Masayasu Yoshino, Robert H. Waterston29, Eric S. Lander30, Jane Rogers26, Ewan Birney, Yoshihide Hayashizaki 
05 Dec 2002-Nature
TL;DR: The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
Abstract: Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences These are clustered into 33,409 'transcriptional units', contributing 901% of a newly established mouse transcriptome database Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome 41% of all transcriptional units showed evidence of alternative splicing In protein-coding transcripts, 79% of splice variations altered the protein product Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics

1,663 citations

Journal ArticleDOI
TL;DR: Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes, supporting immune evasion by altered HLA function as a contributory mechanism in cancer.
Abstract: Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations are enriched for likely functional mutations, including putative loss-of-function events. Recurrence of mutations suggested that these 'hotspot' sites were positively selected. Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes, supporting immune evasion by altered HLA function as a contributory mechanism in cancer.

518 citations

Journal ArticleDOI
TL;DR: This review presents critically the analytical techniques which are used for authenticity assessment, explaining how and why they give plausible solutions, and discusses current limits and gaps, related to informatics needs for data analysis of large quantities.
Abstract: Food authentication is a rapidly growing field due to increasing public awareness concerning food quality and safety. This review presents critically the analytical techniques which are used for authenticity assessment, explaining how and why they give plausible solutions. Classification of different methodologies is based on authenticity indicators providing insight into future developments. Analytical breakthroughs and novel techniques that emerged recently are discussed, along with their applications on food authentication. We have discussed current limits and gaps, related to informatics needs for data analysis of large quantities. Reporting standards and reference database are elaborated indicating urgent needs for the progress of this field. A scientometric evaluation highlighted the research trends and emerging approaches of this evolving field. Popular analytical techniques are commented, while the potential of the field is depicted in the temporal evolution of the research output focusing on geographical distribution of research activity and preferred journals used for dissemination.

374 citations

Journal ArticleDOI
TL;DR: A bioinformatic method was developed for the prediction of peptide binding to MHC class II molecules and its application to the identification of potential immunotherapeutic peptides illustrates the synergy between experimentation and computer modeling.
Abstract: Motivation: Prediction methods for identifying binding peptides could minimize the number of peptides required to be synthesized and assayed, and thereby facilitate the identification of potential T-cell epitopes. We developed a bioinformatic method for the prediction of peptide binding to MHC class II molecules. Results: Experimental binding data and expert knowledge of anchor positions and binding motifs were combined with an evolutionary algorithm (EA) and an artificial neural network (ANN): binding data extraction --> peptide alignment --> ANN training and classification. This method, termed PERUN, was implemented for the prediction of peptides that bind to HLA-DR4(B1*0401). The respective positive predictive values of PERUN predictions of high-, moderate-, low- and zero-affinity binder-a were assessed as 0.8, 0.7, 0.5 and 0.8 by cross-validation, and 1.0, 0.8, 0.3 and 0.7 by experimental binding. This illustrates the synergy between experimentation and computer modeling, and its application to the identification of potential immunotheraaeutic peptides.

333 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal Article
TL;DR: This book by a teacher of statistics (as well as a consultant for "experimenters") is a comprehensive study of the philosophical background for the statistical design of experiment.
Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

13,333 citations

Journal ArticleDOI
Robert H. Waterston1, Kerstin Lindblad-Toh2, Ewan Birney, Jane Rogers3  +219 moreInstitutions (26)
05 Dec 2002-Nature
TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Abstract: The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

6,643 citations

Journal ArticleDOI
03 Apr 2015-Science
TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
Abstract: Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti–PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.

6,215 citations

Journal ArticleDOI
14 Jun 2007-Nature
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

5,091 citations