Vetle I Torvik

Publications of Vetle I Torvik

• MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects.

  Authors: Neil R Smalheiser, Giovanni Lugli, Hooriyah S Rizavi, Vetle I Torvik, Gustavo Turecki, Yogesh Dwivedi

  PloS one. 01/2012; 7(3):e33201.

  Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs)Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases. The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5'-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group. The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).

• Distribution of “Characteristic” Terms in MEDLINE Literatures

  Authors: Neil R Smalheiser, Zhou Wei, Vetle I Torvik

  Information. 01/2011;

  Given the occurrence frequency of any term within any set of articles within MEDLINE, we define “characteristic” terms as words and phrases that occur in that literature more frequently than expectedGiven the occurrence frequency of any term within any set of articles within MEDLINE, we define “characteristic” terms as words and phrases that occur in that literature more frequently than expected by chance (at p < 0.001 or better). In this report, we studied how the cut-off criterion varied as a function of literature size and term frequency in MEDLINE as a whole, and have compared the distribution of characteristic terms within a number of journal-defined, affiliation-defined and random literatures. We also investigated how the characteristic terms were distributed among MEDLINE titles, abstracts, and last sentence of abstracts, including “regularized” terms that appear both in the title and abstract of the same paper for at least one paper in the literature. For a set of 10 disciplinary journals, the characteristic terms comprised 18% of the total terms on average. Characteristic terms are utilized in several of our web-based services (Anne O’Tate and Arrowsmith), and should be useful for a variety of other information-processing tasks designed to improve text mining in MEDLINE.

• MicroRNA expression in rat brain exposed to repeated inescapable shock: differential alterations in learned helplessness vs. non-learned helplessness.

  Authors: Neil R Smalheiser, Giovanni Lugli, Hooriyah S Rizavi, Hui Zhang, Vetle I Torvik, Ghanshyam N Pandey, John M Davis, Yogesh Dwivedi

  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 01/2011; 14(10):1315-25.

  MicroRNA (miRNA) expression was measured within frontal cortex of male Holtzman rats subjected to repeated inescapable shocks at days 1 and 7, tested for learned helplessness (LH) at days 2 and 8,MicroRNA (miRNA) expression was measured within frontal cortex of male Holtzman rats subjected to repeated inescapable shocks at days 1 and 7, tested for learned helplessness (LH) at days 2 and 8, and sacrificed at day 15. We compared rats that did vs. did not exhibit LH, as well as rats that were placed in the apparatus and tested for avoidance but not given shocks (tested controls, TC). Non-learned helpless (NLH) rats showed a robust adaptive miRNA response to inescapable shock whereas LH rats showed a markedly blunted response. One set of 12 miRNAs showed particularly large, significant down-regulation in NLH rats relative to tested controls (mir-96, 141, 182, 183, 183*, 298, 200a, 200a*, 200b, 200b*, 200c, 429). These were encoded at a few shared polycistronic loci, suggesting that the down-regulation was coordinately controlled at the level of transcription. Most of these miRNAs are enriched in synaptic fractions. Moreover, almost all of these share 5'-seed motifs with other members of the same set, suggesting that they will hit similar or overlapping sets of target mRNAs. Finally, half of this set is predicted to hit Creb1 as a target. We also identified a core miRNA co-expression module consisting of 36 miRNAs that are highly correlated with each other across individuals of the LH group (but not in the NLH or TC groups). Thus, miRNAs participate in the alterations of gene expression networks that underlie the normal (NLH) as well as aberrant (LH) response to repeated shocks.

• Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus.

  Authors: Neil R Smalheiser, Giovanni Lugli, Angela L Lenon, John M Davis, Vetle I Torvik, John Larson

  ASN neuro. 01/2010; 2(1):e00028.

  Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination trainingAdult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of approximately 40 min of training). The hippocampus was dissected bilaterally from each mouse (N = 7 in each group) and profiling of 585 miRNAs (microRNAs) was carried out using multiplex RT-PCR (reverse transcription-PCR) plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P = 0.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor), CAMK2b (calcium/calmodulin-dependent protein kinase IIβ), CREB1 (cAMP-response-element-binding protein 1) and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

• Author Name Disambiguation in MEDLINE.

  Authors: Vetle I Torvik, Neil R Smalheiser

  ACM transactions on knowledge discovery from data. 07/2009; 3(3).

  BACKGROUND: We recently described "Author-ity," a model for estimating the probability that two articles in MEDLINE, sharing the same author name, were written by the same individual. FeaturesBACKGROUND: We recently described "Author-ity," a model for estimating the probability that two articles in MEDLINE, sharing the same author name, were written by the same individual. Features include shared title words, journal name, coauthors, medical subject headings, language, affiliations, and author name features (middle initial, suffix, and prevalence in MEDLINE). Here we test the hypothesis that the Author-ity model will suffice to disambiguate author names for the vast majority of articles in MEDLINE. METHODS: Enhancements include: (a) incorporating first names and their variants, email addresses, and correlations between specific last names and affiliation words; (b) new methods of generating large unbiased training sets; (c) new methods for estimating the prior probability; (d) a weighted least squares algorithm for correcting transitivity violations; and (e) a maximum likelihood based agglomerative algorithm for computing clusters of articles that represent inferred author-individuals. RESULTS: Pairwise comparisons were computed for all author names on all 15.3 million articles in MEDLINE (2006 baseline), that share last name and first initial, to create Author-ity 2006, a database that has each name on each article assigned to one of 6.7 million inferred author-individual clusters. Recall is estimated at ~98.8%. Lumping (putting two different individuals into the same cluster) affects ~0.5% of clusters, whereas splitting (assigning articles written by the same individual to >1 cluster) affects ~2% of articles. IMPACT: The Author-ity model can be applied generally to other bibliographic databases. Author name disambiguation allows information retrieval and data integration to become person-centered, not just document-centered, setting the stage for new data mining and social network tools that will facilitate the analysis of scholarly publishing and collaboration behavior. AVAILABILITY: The Author-ity 2006 database is available for nonprofit academic research, and can be freely queried via http://arrowsmith.psych.uic.edu.

• Arrowsmith two-node search interface: A tutorial on finding meaningful links between two disparate sets of articles in MEDLINE.

  Authors: Neil R Smalheiser, Vetle I Torvik, Wei Zhou

  Computer methods and programs in biomedicine. 02/2009;

  The Arrowsmith two-node search is a strategy that is designed to assist biomedical investigators in formulating and assessing scientific hypotheses. More generally, it allows users to identifyThe Arrowsmith two-node search is a strategy that is designed to assist biomedical investigators in formulating and assessing scientific hypotheses. More generally, it allows users to identify biologically meaningful links between any two sets of articles A and C in PubMed, even when these share no articles or authors in common and represent disparate topics or disciplines. The key idea is to relate the two sets of articles via title words and phrases (B-terms) that they share. We have created a free, public web-based version of the two-node search tool (http://arrowsmith.psych.uic.edu), have described its development and implementation, and have presented analyses of individual two-node searches. In this paper, we provide an updated tutorial intended for end-users, that covers the use of the tool for a variety of potential scientific use case scenarios. For example, one can assess a recent experimental, clinical or epidemiologic finding that connects two disparate fields of inquiry-identifying likely mechanisms to explain the finding, and choosing promising follow-up lines of investigation. Alternatively, one can assess whether the existing scientific literature lends indirect support to a hypothesis posed by the user that has not yet been investigated. One can also employ two-node searches to search for novel hypotheses. Arrowsmith provides a service that cannot be carried out feasibly via standard PubMed searches or by other available text mining tools.

• Author name disambiguation.

  Authors: Neil R. Smalheiser, Vetle I. Torvik

  ARIST. 01/2009; 43:1-43.

• Author name disambiguation in MEDLINE.

  Authors: Vetle I. Torvik, Neil R. Smalheiser

  TKDD. 01/2009; 3.

• Natural antisense transcripts are co-expressed with sense mRNAs in synaptoneurosomes of adult mouse forebrain.

  Authors: Neil R Smalheiser, Giovanni Lugli, Vetle I Torvik, Nathan Mise, Rieko Ikeda, Kuniya Abe

  Neuroscience research. 10/2008;

  Natural antisense transcripts and overlapping sense transcripts are expressed in a variety of tissues, including adult mouse brain. Here we show that a subset of mRNA-like sense-antisense transcriptNatural antisense transcripts and overlapping sense transcripts are expressed in a variety of tissues, including adult mouse brain. Here we show that a subset of mRNA-like sense-antisense transcript pairs are co-expressed within synaptoneurosomes of adult mouse forebrain, a subcellular fraction that is enriched in pinched-off dendritic spines of pyramidal neurons. Several of these pairs involve mRNAs that have been implicated in synaptic functions and in Alzheimer disease pathways. This study provides evidence that a new class of noncoding RNAs (natural antisense transcripts) are expressed near synapses, and encourages further studies of their roles in neuronal function.

• Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain.

  Authors: Giovanni Lugli, Vetle I Torvik, John Larson, Neil R Smalheiser

  Journal of neurochemistry. 06/2008;

  We have characterized the expression of microRNAs and selected microRNA precursors within several synaptic fractions of adult mouse forebrain, including synaptoneurosomes, synaptosomes and isolatedWe have characterized the expression of microRNAs and selected microRNA precursors within several synaptic fractions of adult mouse forebrain, including synaptoneurosomes, synaptosomes and isolated post-synaptic densities (PSDs), using methods of microRNA microarray, real time qRT-PCR, Northern blotting and immunopurification using anti-PSD95 antibody. The majority of brain microRNAs (especially microRNAs known to be expressed in pyramidal neurons) are detectably expressed in synaptic fractions, and a subset of microRNAs is significantly enriched in synaptic fractions relative to total forebrain homogenate. MicroRNA precursors are also detectable in synaptic fractions at levels that are comparable to whole tissue. Whereas mature microRNAs are predominantly associated with soluble components of the synaptic fractions, microRNA precursors are predominantly associated with PSDs. For seven microRNAs examined, there was a significant correlation between the relative synaptic enrichment of the precursor and the relative synaptic enrichment of the corresponding mature microRNA. These findings support the proposal that microRNAs are formed, at least in part, via processing of microRNA precursors locally within dendritic spines. Dicer is expressed in PSDs but is enzymatically inactive until conditions that activate calpain cause its liberation; thus, we propose that synaptic stimulation may lead to local processing of microRNA precursors in proximity to the synapse.

• Anne O'Tate: A tool to support user-driven summarization, drill-down and browsing of PubMed search results.

  Authors: Neil R Smalheiser, Wei Zhou, Vetle I Torvik

  Journal of biomedical discovery and collaboration. 02/2008; 3:2.

  ABSTRACT: BACKGROUND: PubMed is designed to provide rapid, comprehensive retrieval of papers that discuss a given topic. However, because PubMed does not organize the search output further, it isABSTRACT: BACKGROUND: PubMed is designed to provide rapid, comprehensive retrieval of papers that discuss a given topic. However, because PubMed does not organize the search output further, it is difficult for users to grasp an overview of the retrieved literature according to non-topical dimensions, to drill-down to find individual articles relevant to a particular individual's need, or to browse the collection. RESULTS: In this paper, we present Anne O'Tate, a web-based tool that processes articles retrieved from PubMed and displays multiple aspects of the articles to the user, according to pre-defined categories such as the "most important" words found in titles or abstracts; topics; journals; authors; publication years; and affiliations. Clicking on a given item opens a new window that displays all papers that contain that item. One can navigate by drilling down through the categories progressively, e.g., one can first restrict the articles according to author name and then restrict that subset by affiliation. Alternatively, one can expand small sets of articles to display the most closely related articles. We also implemented a novel cluster-by-topic method that generates a concise set of topics covering most of the retrieved articles. CONCLUSION: Anne O'Tate is an integrated, generic tool for summarization, drill-down and browsing of PubMed search results that accommodates a wide range of biomedical users and needs. It can be accessed at 4. Peer review and editorial matters for this article were handled by Aaron Cohen.

• A quantitative model for linking two disparate sets of articles in MEDLINE.

  Authors: Vetle I Torvik, Neil R Smalheiser

  Bioinformatics (Oxford, England). 08/2007; 23(13):1658-65.

  BACKGROUND: Identifying information that implicitly links two disparate sets of articles is a fundamental and intuitive data mining strategy that can help investigators address real scientificBACKGROUND: Identifying information that implicitly links two disparate sets of articles is a fundamental and intuitive data mining strategy that can help investigators address real scientific questions. The Arrowsmith two-node search finds title words and phrases (so-called B-terms) that are shared across two sets of articles within MEDLINE and displays them in a manner that facilitates human assessment. A serious stumbling-block has been the lack of a quantitative model for predicting which of the hundreds if not thousands of B-terms computed for a given search are most likely to be relevant to the investigator. METHODOLOGY/PRINCIPAL FINDINGS: Using a public two-node search interface, field testers devised a set of two-node searches under real life conditions and a certain number of B-terms were marked relevant. These were employed as 'gold standards;' each B-term was characterized according to eight complementary features that were strongly correlated with relevance. A logistic regression model was developed that permits one to estimate the probability of relevance for each B-term, to rank B-terms according to their likely relevance, and to estimate the overall number of relevant B-terms inherent in a given two-node search. CONCLUSIONS/SIGNIFICANCE: The model greatly simplifies and streamlines the process of carrying out a two-node search, and may be applicable to a number of other literature-based discovery applications, including the so-called one-node search and related gene-centric strategies that incorporate implicit links to predict how genes may be related to each other and to human diseases. This should encourage much wider exploration of text mining for implicit information among the general scientific community. AVAILABILITY: Two-node searches can be carried out freely at http://arrowsmith.psych.uic.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

• Knowledge-intensive conceptual retrieval and passage extraction of biomedical literature.

  Authors: Wei Zhou, Clement T. Yu, Neil R. Smalheiser, Vetle I. Torvik, Jie Hong

  SIGIR 2007: Proceedings of the 30th Annual International ACM SIGIR Conference on Research and Development in Information Retrieval, Amsterdam, The Netherlands, July 23-27, 2007; 01/2007

• ADAM: another database of abbreviations in MEDLINE.

  Authors: Wei Zhou, Vetle I Torvik, Neil R Smalheiser

  Bioinformatics (Oxford, England). 12/2006; 22(22):2813-8.

  MOTIVATION: Abbreviations are an important type of terminology in the biomedical domain. Although several groups have already created databases of biomedical abbreviations, these are either notMOTIVATION: Abbreviations are an important type of terminology in the biomedical domain. Although several groups have already created databases of biomedical abbreviations, these are either not public, or are not comprehensive, or focus exclusively on acronym-type abbreviations. We have created another abbreviation database, ADAM, which covers commonly used abbreviations and their definitions (or long-forms) within MEDLINE titles and abstracts, including both acronym and non-acronym abbreviations. RESULTS: A model of recognizing abbreviations and their long-forms from titles and abstracts of MEDLINE (2006 baseline) was employed. After grouping morphological variants, 59 405 abbreviation/long-form pairs were identified. ADAM shows high precision (97.4%) and includes most of the frequently used abbreviations contained in the Unified Medical Language System (UMLS) Lexicon and the Stanford Abbreviation Database. Conversely, one-third of abbreviations in ADAM are novel insofar as they are not included in either database. About 19% of the novel abbreviations are non-acronym-type and these cover at least seven different types of short-form/long-form pairs. AVAILABILITY: A free, public query interface to ADAM is available at http://arrowsmith.psych.uic.edu, and the entire database can be downloaded as a text file.

• Alu elements within human mRNAs are probable microRNA targets.

  Authors: Neil R Smalheiser, Vetle I Torvik

  Trends in genetics : TIG. 11/2006; 22(10):532-6.

  Recently, we reported that four microRNAs show perfect complementarity with MIR/LINE-2 elements within human mRNAs. This finding raises the question of whether microRNAs might also target otherRecently, we reported that four microRNAs show perfect complementarity with MIR/LINE-2 elements within human mRNAs. This finding raises the question of whether microRNAs might also target other genomic repeats and transposable elements. Here, we demonstrate that almost 30 human microRNAs exhibit typical short-seed complementarity with a specific site within Alu elements that is highly conserved within 3' untranslated regions of human mRNAs. The results suggest that at least some Alu elements within human mRNAs serve as microRNA targets.

• Collaborative development of the Arrowsmith two node search interface designed for laboratory investigators.

  Authors: Neil R Smalheiser, Vetle I Torvik, Amanda Bischoff-Grethe, Lauren B Burhans, Michael Gabriel, Ramin Homayouni, Alireza Kashef, Maryann E Martone, Guy A Perkins, Diana L Price, Andrew C Talk, Ruth West

  Journal of biomedical discovery and collaboration. 02/2006; 1:8.

  Arrowsmith is a unique computer-assisted strategy designed to assist investigators in detecting biologically-relevant connections between two disparate sets of articles in Medline. This paperArrowsmith is a unique computer-assisted strategy designed to assist investigators in detecting biologically-relevant connections between two disparate sets of articles in Medline. This paper describes how an inter-institutional consortium of neuroscientists used the UIC Arrowsmith web interface http://arrowsmith.psych.uic.edu in their daily work and guided the development, refinement and expansion of the system into a suite of tools intended for use by the wider scientific community.

• Complications in mammalian microRNA target prediction.

  Authors: Neil R Smalheiser, Vetle I Torvik

  Methods in molecular biology (Clifton, N.J.). 02/2006; 342:115-27.

  In this chapter, we review evidence that at least three different types of microRNA (miRNA)-messenger RNA (mRNA) target interactions exist in mammals: short seeds, long seeds, and "perfect" hitsIn this chapter, we review evidence that at least three different types of microRNA (miRNA)-messenger RNA (mRNA) target interactions exist in mammals: short seeds, long seeds, and "perfect" hits (allowing G:U matches). Because new types of miRNAs are still being discovered, this list may not yet be complete.

• Segmentation of Publication Records of Authors from the Web.

  Authors: Wei Zhang, Clement T. Yu, Neil R. Smalheiser, Vetle I. Torvik

  Proceedings of the 22nd International Conference on Data Engineering, ICDE 2006, 3-8 April 2006, Atlanta, GA, USA; 01/2006

• Ranking indirect connections in literature-based discovery: The role of medical subject headings.

  Authors: Don R. Swanson, Neil R. Smalheiser, Vetle I. Torvik

  JASIST. 01/2006; 57:1427-1439.

• A Concept-Based Framework for Passage Retrieval at Genomics.

  Authors: Wei Zhou, Clement T. Yu, Vetle I. Torvik, Neil R. Smalheiser

  Proceedings of the Fifteenth Text REtrieval Conference, TREC 2006, Gaithersburg, Maryland, November 14-17, 2006; 01/2006