Igor Kurochkin - Academia.edu (original) (raw)

Papers by Igor Kurochkin

The Molecular Biology Society of Japan, Oct 30, 2015

Nature, 2002

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts.... more 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 90.1% 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. The FANTOM2 clone set The cDNA clones used in the project were selected from 246 fulllength enriched cDNA libraries, most of which were also normalized and subtracted, with most from C57BL/6J mice, as described elsewhere 12,14,15. Information about tissue source and other information regarding these libraries is available in Supplementary Information section 1. 1,442,236 sequences were grouped into 171,144 3 0-end clusters articles

Scientific Reports, May 29, 2015

Oxidative stress (OS) is caused by an imbalance between pro-and anti-oxidant reactions leading to... more Oxidative stress (OS) is caused by an imbalance between pro-and anti-oxidant reactions leading to accumulation of reactive oxygen species within cells. We here investigate the effect of OS on the transcriptome of human fibroblasts. OS causes a rapid and transient global induction of transcription characterized by pausing of RNA polymerase II (PolII) in both directions, at specific promoters, within 30 minutes of the OS response. In contrast to protein-coding genes, which are commonly down-regulated, this novel divergent, PolII pausing-phenomenon leads to the generation of thousands of long noncoding RNAs (lncRNAs) with promoter-associated antisense lncRNAs transcripts (si-paancRNAs) representing the major group of stress-induced transcripts. OS causes transient dynamics of si-lncRNAs in nucleus and cytosol, leading to their accumulation at polysomes, in contrast to mRNAs, which get depleted from polysomes. We propose that si-lncRNAs represent a novel component of the transcriptional stress that is known to determine the outcome of immediateearly and later cellular stress responses and we provide insights on the fate of those novel mature lncRNA transcripts by showing that their association with polysomal complexes is significantly increased in OS. A large proportion of the human genome is pervasively transcribed producing a great variation of RNA species with little (or no) protein-coding ability. RNA transcripts longer than 200 nt are classified as long non-coding RNAs (lncRNAs) 1,2. Compared with protein-coding genes, lncRNAs show little evolutionary conservation in sequence and have limited coding potential, as indicated by the lack of significant open reading frames (ORFs), typical initiation codon, 3'-untranslated regions (UTRs) and termination codon 3. Moreover, lncRNAs expression is detected at significantly lower levels and is more tissue specific. However, lncRNAs share many features of mRNAs as they are frequently transcribed by RNA polymerase

Genome Research, 2003

FACTS (Functional Association/Annotation of cDNA Clones from Text/Sequence Sources) is a semiauto... more FACTS (Functional Association/Annotation of cDNA Clones from Text/Sequence Sources) is a semiautomated knowledge discovery and annotation system that integrates molecular function information derived from sequence analysis results (sequence inferred) with functional information extracted from text. Text-inferred information was extracted from keyword-based retrievals of MEDLINE abstracts and by matching of gene or protein names to OMIM, BIND, and DIP database entries. Using FACTS, we found that 47.5% of the 60,770 RIKEN mouse cDNA FANTOM2 clone annotations were informative for text searches. MEDLINE queries yielded molecular interaction-containing sentences for 23.1% of the clones. When disease MeSH and GO terms were matched with retrieved abstracts, 22.7% of clones were associated with potential diseases, and 32.5% with GO identifiers. A significant number (23.5%) of disease MeSH-associated clones were also found to have a hereditary disease association (OMIM Morbidmap). Inferred n...

It was more than a decade ago that the first draft of the essentially complete human genome was p... more It was more than a decade ago that the first draft of the essentially complete human genome was published at a result of a coordinated international scientific effort. Whereas the presentation of the draft was celebrated with great pomp, the reviews summarizing the achievements of ten years life science research based on the available human genome sequence hardly made it into the headlines. Not surprisingly, the outcome with regard to cures for not yet treatable diseases or new biotechnologies has not nearly reached the expectations. For the insider, this development was not a major surprise. In 2001, about half of the known protein-coding genes in human was functionally not characterized and, although our biological knowledge is as large as never before in human history, the list of known gene function has not become much longer in the mean time. Protein coding segments constitute only ~1.5% of the human genome but the rest (98.5%) is also actively transcribed and apparently functi...

情報処理学会研究報告自然言語処理研究会報告, Jan 13, 2004

The list of enriched cellular component gene ontologies in pairwise comparisons between all analy... more The list of enriched cellular component gene ontologies in pairwise comparisons between all analyzed subcellular fractions. (XLSX 11 kb)

The list of differentially expressed RNAs in PX and IP fractions as compared to total cellular RN... more The list of differentially expressed RNAs in PX and IP fractions as compared to total cellular RNA fraction (T) with a fold change cut-off more that 2-times. (XLSX 32 kb)

The integrated list of mRNAs enriched in peroxisomes and proteins detected in peroxisomes by mass... more The integrated list of mRNAs enriched in peroxisomes and proteins detected in peroxisomes by mass spectrometry. (XLS 143 kb)

Normalization of microarray data by invariant gene set. (A) Background-corrected mRNA expression ... more Normalization of microarray data by invariant gene set. (A) Background-corrected mRNA expression across the technical replicas of the mRNA sample fractions. (B) Background-corrected mRNA expression across the technical replicas of the mRNA sample fractions. (C) Expression of the invariant genes across the technical replicas of the mRNA sample fractions. (D) Gene expression after normalization by the invariant gene set. (PPTX 53 kb)

Loadings of the variance principal components of the mRNA microarray data. (PPTX 34 kb)

Frontiers in Genetics, 2015

Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer th... more Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. They constitute a major, but still poorly characterized part of human transcriptome, however, evidence is growing that they are important regulatory molecules involved in various cellular processes. It is becoming increasingly clear that many lncRNAs are deregulated in cancer and some of them can be important drivers of malignant transformation. On the one hand, some lncRNAs can have highly specific expression in particular types of cancer making them a promising tool for diagnosis. The expression of other lncRNAs can correlate with different pathophysiological features of tumor growth and with patient survival, thus making them convenient biomarkers for prognosis. In this review we outline the current state of knowledge about the fast growing field of application of lncRNAs as tumor biomarkers.

Science (New York, N.Y.), 2005

This study describes comprehensive polling of transcription start and termination sites and analy... more 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.

BMC Bioinformatics, 2008

Background The import of most intraperoxisomal proteins is mediated by peroxisome targeting signa... more Background The import of most intraperoxisomal proteins is mediated by peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions (PTS2). Both signals have been integrated in subcellular location prediction programs. However their present performance, particularly of PTS2-targeting did not seem fitting for large-scale screening of sequences. Results We modified an earlier reported PTS1 screening method to identify PTS2-containing mouse candidates using a combination of computational and manual annotation. For rapid confirmation of five new PTS2- and two previously identified PTS1-containing candidates we developed the new cell line CHO-perRed which stably expresses the peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal localization of PTS1-targeted candidate Zadh2. Preliminary characterization of Zadh2 expression suggested non-PPARα mediated activation. Notably, none of the PTS2 candidates located to peroxisomes. Conclusion In a few cases ...

Cell Structure and Function, 2000

Insulin-degrading enzyme (IDE) was detected by immunoblot analysis in highly purified rat liver p... more Insulin-degrading enzyme (IDE) was detected by immunoblot analysis in highly purified rat liver peroxisomes. IDE in the peroxisomal fraction was resistant to proteolysis by trypsin and chymotrypsin under conditions where the peroxisomal membranes remained intact. After sonication of the peroxisomal fraction, IDE was recovered in the supernatant fraction. Further, the localization of IDE in the peroxisomes was shown by immunoelectron microscopy. In addition, IDE isolated from peroxisomes degraded insulin as well as oxidized lysozyme as a model substrate for oxidized proteins. These results suggest that IDE exists in an active form in the matrix of rat liver peroxisomes and is involved in elimination of oxidized proteins in peroxisomes.

The LHC has two dedicated cleaning insertions: IR3 for momentum cleaning and IR7 for betatron cle... more The LHC has two dedicated cleaning insertions: IR3 for momentum cleaning and IR7 for betatron cleaning. The collimation system has been specified and built with tight mechanical tolerances (e.g. jaw flatness ~ 40 μm) and is designed to achieve a high accuracy and reproducibility of the jaw positions. The practically achievable cleaning efficiency of the present Phase-I system depends on the precision of the jaw centering around the beam, the accuracy of the gap size and the jaw parallelism against the beam. The reproducibility and stability of the system is important to avoid the frequent repetition of beam based alignment which is currently a lengthy procedure. Within this paper we describe the method used for the beam based alignment of the LHC collimation system, its achieved accuracy and stability and its performance at 450GeV.

Scientific reports, Jan 29, 2015

Oxidative stress (OS) is caused by an imbalance between pro- and anti-oxidant reactions leading t... more Oxidative stress (OS) is caused by an imbalance between pro- and anti-oxidant reactions leading to accumulation of reactive oxygen species within cells. We here investigate the effect of OS on the transcriptome of human fibroblasts. OS causes a rapid and transient global induction of transcription characterized by pausing of RNA polymerase II (PolII) in both directions, at specific promoters, within 30 minutes of the OS response. In contrast to protein-coding genes, which are commonly down-regulated, this novel divergent, PolII pausing-phenomenon leads to the generation of thousands of long noncoding RNAs (lncRNAs) with promoter-associated antisense lncRNAs transcripts (si-paancRNAs) representing the major group of stress-induced transcripts. OS causes transient dynamics of si-lncRNAs in nucleus and cytosol, leading to their accumulation at polysomes, in contrast to mRNAs, which get depleted from polysomes. We propose that si-lncRNAs represent a novel component of the transcriptiona...

We have developed a toolkit in which an annotation tool, a syntactic tree editor, and an extracti... more We have developed a toolkit in which an annotation tool, a syntactic tree editor, and an extraction rule editor interact dynamically. Its output can be stored in a database for further use. In the field of biomedicine, there is a critical need for automatic text processing. However, current language processing approaches suffer from insufficient basic data incorporating both human domain expertise and domain-specific language processing capabilities. With the annotation tool presented here, a set of “gold standards” can be collected, representing what should be extracted. At the same time, any change in annotation can be viewed on an associated syntactic tree. These facilities provide a clear picture of the relationship between the extraction target and the syntactic tree. Underlying sentences can be analyzed with a parser which can be plugged in, or a set of parsed sentences can be used to generate the tree. Extraction rules written with the integrated editor can be applied at once...