The TREC 2004 genomics track categorization task: classifying full text biomedical documents

Background

The TREC 2004 Genomics Track focused on applying information retrieval and text mining techniques to improve the use of genomic information in biomedicine. The Genomics Track consisted of two main tasks, ad hoc retrieval and document categorization. In this paper, we describe the categorization task, which focused on the classification of full-text documents, simulating the task of curators of the Mouse Genome Informatics (MGI) system and consisting of three subtasks. One subtask of the categorization task required the triage of articles likely to have experimental evidence warranting the assignment of GO terms, while the other two subtasks were concerned with the assignment of the three top-level GO categories to each paper containing evidence for these categories.

Results

The track had 33 participating groups. The mean and maximum utility measure for the triage subtask was 0.3303, with a top score of 0.6512. No system was able to substantially improve results over simply using the MeSH term Mice. Analysis of significant feature overlap between the training and test sets was found to be less than expected. Sample coverage of GO terms assigned to papers in the collection was very sparse. Determining papers containing GO term evidence will likely need to be treated as separate tasks for each concept represented in GO, and therefore require much denser sampling than was available in the data sets.The annotation subtask had a mean F-measure of 0.3824, with a top score of 0.5611. The mean F-measure for the annotation plus evidence codes subtask was 0.3676, with a top score of 0.4224. Gene name recognition was found to be of benefit for this task.

Conclusion

Automated classification of documents for GO annotation is a challenging task, as was the automated extraction of GO code hierarchies and evidence codes. However, automating these tasks would provide substantial benefit to biomedical curation, and therefore work in this area must continue. Additional experience will allow comparison and further analysis about which algorithmic features are most useful in biomedical document classification, and better understanding of the task characteristics that make automated classification feasible and useful for biomedical document curation. The TREC Genomics Track will be continuing in 2005 focusing on a wider range of triage tasks and improving results from 2004.

     

Applied information retrieval and multidisciplinary research: new mechanistic hypotheses in Complex Regional Pain Syndrome

Background

Collaborative efforts of physicians and basic scientists are often necessary in the investigation of complex disorders. Difficulties can arise, however, when large amounts of information need to reviewed. Advanced information retrieval can be beneficial in combining and reviewing data obtained from the various scientific fields. In this paper, a team of investigators with varying backgrounds has applied advanced information retrieval methods, in the form of text mining and entity relationship tools, to review the current literature, with the intention to generate new insights into the molecular mechanisms underlying a complex disorder. As an example of such a disorder the Complex Regional Pain Syndrome (CRPS) was chosen. CRPS is a painful and debilitating syndrome with a complex etiology that is still unraveled for a considerable part, resulting in suboptimal diagnosis and treatment.

Results

A text mining based approach combined with a simple network analysis identified Nuclear Factor kappa B (NFκB) as a possible central mediator in both the initiation and progression of CRPS.

Conclusion

The result shows the added value of a multidisciplinary approach combined with information retrieval in hypothesis discovery in biomedical research. The new hypothesis, which was derived in silico, provides a framework for further mechanistic studies into the underlying molecular mechanisms of CRPS and requires evaluation in clinical and epidemiological studies.

     

Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome

Background

Graham Little – Piccardi – Lassueur (GLPL) syndrome is a rare dermatosis characterized by scarring alopecia, loss of pubic and axillary hair, and progressive development of variously located follicular papules. We report a first case ever of an autoimmune response in a patient suffering from GLPL syndrome.

Methods

Immunofluorescence and immunoblot analysis were used in a variety of cell cultures including human, monkey, hamster, mouse and bovine cells to analyze the presence of autoantibodies in a GLPL patient.

Results

The autoimmune serum showed a pattern of centromere and spindle microtubule staining resembling that of the chromosomal passenger protein complex. By using a complex of proteins expressed in baculovirus, immunoblot analysis demonstrated that the INCENP protein is a major autoantigen in this patient with GLPL syndrome.

Conclusion

An autoimmune response in GLPL syndrome is reported against the INCENP centromere protein. The occasional development of autoimmunity in GLPL patients could serve as a test in continuing efforts to detect this disease and for a more directed therapy based on the autoantigen response.

     

Prevalence of antibodies to Ro-52 in a serologically defined population of patients with systemic sclerosis

Background

Antibodies against Ro-52 have been described in patients with a broad spectrum of autoimmune disease, most commonly in association with anti-Ro-60 in systemic lupus erythematosus and Sjogrens syndrome. However, in inflammatory myositis anti-Ro-52 is frequently present without anti-Ro-60 and is closely linked to the presence of aminoacyl-tRNA synthetase (aats) antibodies. To date there have been no comprehensive reports on the frequency of anti-Ro-52 in systemic sclerosis (SSc), a disease characterised by hallmark autoantibodies that occur in non-overlapping subsets. Clinically, each antibody-defined group has a distinct pattern of organ involvement, some featuring myositis.

Objectives

To determine the frequency of anti-Ro-52 in serologically defined groups of SSc patients and to investigate a possible link with myositis-associated autoantibodies.

Methods

Serum samples from 1010 patients with SSc and 55 and 32 patients with anti-aats and anti-Ku respectively were tested for the presence of anti-Ro-52 using a commercial ELISA.

Results

The prevalence of anti-Ro-52 was 15–38% in nine of the eleven sub-groups. There were no significant differences in mean anti-Ro-52 levels in these groups with the exception of that defined by the presence of anti-U1-RNP. In the remaining groups defined by anti-Ro-60 and anti-aats, anti-Ro-52 was present in 92% and 100% respectively. In sera from non-SSc patients with anti-aats, anti-Ro-52 was detected in 64%.

Conclusion

Anti-Ro-52 is present throughout the SSc population. It is neither more prevalent in the myositis-associated antibody groups nor does it segregate with any other major SSc-specific autoantibodies. The co-existence of anti-Ro-52 with both anti-Ro-60 and anti-aats is confirmed.

     

Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins

Background

Biological organisms and their components are better conceived within categories based on similarity rather than on identity. Biologists routinely operate with similarity-based concepts such as "model organism" and "motif." There has been little exploration of the characteristics of the similarity-based categories that exist in biology. This study uses the case of the discovery and classification of zinc finger proteins to explore how biological categories based in similarity are represented.

Results

The existence of a category of "zinc finger proteins" was based in 1) a lumpy gradient of similarity, 2) a link between function and structure, 3) establishment of a range of appearance across systems and organisms, and 4) an evolutionary locus as a historically based common-ground.

Conclusion

More systematic application of the idea of similarity-based categorization might eliminate the assumption that biological characteristics can only contribute to narrow categorization of humans. It also raises possibilities for refining data-driven exploration efforts.

     

Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes

Background

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4).

Methods

We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction.

Results

Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes.

Conclusion

Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4.

     

Patterns in abundance and diversity of faecally dispersed parasites of tiger in Tadoba National Park,central India

Background

Importance of parasites in ecological and evolutionary interactions is being increasingly recognized. However, ecological data on parasites of important host species is still scanty. We analyze the patterns seen in the faecal parasites of tigers in the Tadoba National Park, India, and speculate on the factors and processes shaping the parasite community and the possible implications for tiger ecology.

Results

The prevalence and intensities were high and the parasite community was dominated by indirect life cycle parasites. Across all genera of parasites variance scaled with the square of the mean and there was a significant positive correlation between prevalence and abundance. There was no significant association between different types of parasites.

Conclusions

The 70 samples analyzed formed 14 distinct clusters. If we assume each of the clusters to represent individual tigers that were sampled repeatedly and that resident tigers are more likely to be sampled repeatedly, the presumed transient tigers had significantly greater parasite loads than the presumed resident ones.

     

Collaboration and distances between German immunological institutes – a trend analysis

Background

The hypothesis that distance matters but that in recent years geographical proximity has become less important for research collaboration was tested. We have chosen a sample–authors at German immunological institutes–that is relatively homogeneous with regard to research field, language and culture, which beside distance are other possible factors influencing the willingness to co-operate. We analyse yearly distributions of co-authorship links between institutes and compare them with the yearly distributions of distances of all institutes producing papers in journals indexed in the Science Citation Index, editions 1992 till 2002. We weight both types of distributions properly with paper numbers.

Results

One interesting result is that place matters but if a researcher has to leave the home town to find a collaborator distance does not matter any longer. This result holds for all years considered, but is statistically most significant in 2002. The tendency to leave the own town for collaborators has slightly increased in the sample. In addition, yearly productivity distributions of institutes have been found to be lognormal.

Conclusion

The Internet did not change much the collaboration patterns between German immunological institutes.

     

Co-occurrence of autoimmune thyroid disease in a multiple sclerosis cohort

Background

Multiple sclerosis (MS), Hashimoto's disease and Graves' disease are autoimmune diseases that may share similar pathogenic mechanisms. The co-occurrence rates and demographic characteristics of Graves' disease and Hashimoto's disease (HT) in our MS population are compared with the general population.

Methods

The prevalence of thyroid disease in our MS patients was determined by chart review and survey. Previous diagnosis of thyroid disease, age at diagnosis, treatment used, and about the use of disease modifying medications used to treat their MS were asked. Chart reviews were used to estimate the population prevalence of Graves' disease and Hashimoto's disease and to estimate the demographics of patients with thyroid disease.

Results

A significant co-occurrence of Graves' disease with MS (p = 0.002), and a non-significant co-occurrence of Hashimoto's disease were noted (p = 0.097). No difference in the age of onset or gender of thyroid disease in MS patients compared to the general population was found.

Conclusion

There is a significant co-occurrence in patients with MS and Graves' disease, and a trend to co-occurrence in patients with MS and Hashimoto's disease. There are no differences in the demographics of patients with thyroid disease in our MS patients compared to the general population.

     

Non-obstructive azoospermia and maturation arrest with complex translocation 46,XY t(9;13;14)(p22;q21.2;p13) is consistent with the Luciani-Guo hypothesis of latent aberrant autosomal regions and infertility

Objective

To describe clinical and histological features observed in the setting of an unusual complex translocation involving three autosomes (9, 13, and 14) identified in an otherwise healthy male referred for infertility consultation.

Materials and methods

The patient was age 30 and no family history was available (adopted). Total azoospermia was confirmed on multiple semen analyses. Peripheral karyotype showed a 46,XY t(9;13;14)(p22:q21.2;p13) genotype; no Y-chromosome microdeletions were identified. Cystic fibrosis screening was negative. Bilateral testis biopsy revealed uniform maturation arrest and peritubular fibrosis.

Results

Formal genetic counseling was obtained and the extant literature reviewed with the couple. Given the low probability of obtaining sperm on testicular biopsy, as well as the high risk of any retrieved sperm having an unbalanced genetic rearrangement, the couple elected to proceed with fertility treatment using anonymous donor sperm for insemination.

Conclusion

Although genes mapped to the Y-chromosome have been established as critical to normal testicular development and spermatogenesis, certain autosomal genes are now also recognized as important in these processes. Here we present clinical evidence to support the Luciani-Guo hypothesis (first advanced in 1984 and refined in 2002), which predicts severe spermatogenic impairment with aberrations involving chromosomes 9, 13, and/or 14, independent of Y-chromosome status. Additional study including fluorescent in situ hybridization and molecular analysis of specific chromosomal regions is needed to characterize more fully the contribution(s) of these autosomes to male testicular development and spermatogenesis.

     

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

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.

     

Higher yields of hybrid rice do not depend on nitrogen fertilization under moderate to high soil fertility conditions

Background

Increasing rice yield with fewer external inputs is critical to ensuring food security, reducing environmental costs, and improving returns. Use of hybrid rice has expanded greatly in China due to its higher yield potential. Meanwhile, large and increasing amounts of nitrogen (N) fertilizers have been used for expanding rice production in China. It is not clear to what extent the success of hybrid rice in China is associated with N fertilizer inputs.

Findings

We observed that the higher grain yield with N fertilizer in hybrid rice was driven more by a higher yield without N fertilizer than by increases in grain yield with N fertilizer under moderate to high soil fertility conditions.

Conclusions

Our results suggest that greater application of N fertilizers is not needed to benefit from hybrid rice production under moderate to high soil fertility conditions, and that improving and maintaining soil fertility should be a focus for sustaining hybrid rice production. Moreover, our study also indicates that zero-N testing may be a potentially useful tool to develop hybrid rice with high yield and without requirement of greater external N inputs under moderate to high soil fertility conditions.

     

Fox sightings in a city are related to certain land use classes and sociodemographics: results from a citizen science project

Background

Red foxes (Vulpes vulpes L.) have become successful inhabitants of urban areas in recent years. However, our knowledge about the occurrence, distribution and association with land uses of these urban foxes is poor, partly because many favoured habitats are on private properties and therefore hardly accessible to scientists. We assumed that citizen science, i.e. the involvement of the public, could enable researchers to bridge this information gap. We analysed 1179 fox sightings in the city of Vienna, Austria reported via citizen science projects to examine relationships between foxes and the surrounding land use classes as well as sociodemographic parameters.

Results

Conditional probabilities of encountering foxes were substantially higher in gardens, areas with a low building density, parks or squares as compared to agricultural areas, industrial areas or forests. Generalized linear model analyses showed that sociodemographic parameters such as education levels, district area, population density and average household income additionally improved the predictability of fox sightings.

Conclusions

Reports of fox sightings by citizen scientists might help to support the establishment of wildlife management in cities. Additionally, these data could be used to address public health issues in relation with red foxes as they can carry zoonoses that are also dangerous to humans.

     

Autoantigenic nuclear proteins of a clinically atypical renal vasculitis

Background

Systemic vasculitides constitute a heterogeneous group of diseases of autoimmunological origin characterized by inflammation of blood vessels and antibodies that react against autoantigens in a process that ultimately affects blood vessel walls. An important number of these patients present kidney disease. An endeavour of this area of research is the identification of autoantigens involved in these diseases. Accordingly, we used serum from a patient suffering from a microscopic polyangiitis, P-ANCA positive, manifesting a clinically atypical renal necrotizing glomerulonephritis and interstitial nephropathy for the identification of autoantigens; we also determined the prevalence of corresponding autoantibodies in other vasculitides, diabetic microangiopathy and in general population.

Methods

The patient's serum was used as a probe for the immunoscreening method SEREX to screen a human brain cDNA expression library.

Results

Four positive clones were isolated and sequenced. Clones Jos002 code for protein HDAC5, Jos014 for TFC4, Jos107 for RTF1, and Jos313 for POLDIP3 polymerase. The four proteins are of nuclear localization. None of them had been reported as autoantigen. Recombinant proteins were synthesised and checked as antigens by western blot with different sera from controls and patients affected with other vasculitides and diabetic microangiopathy as well. Only the serum from the patient origin of this study recognized all recombinant proteins.

Conclusion

We identify four nuclear proteins, HDAC5, TFC4, RTF1 and POLDIP3 polymerase as new autoantigens that could be used as markers in the diagnosis of subfamilies in immune diseases, although we cannot determine the role of these proteins in the aetiopathogenic process.

     

Are classification criteria for vasculitis useful in clinical practice? Observations and lessons from Colombia

Introduction

Idiopathic systemic vasculitis represents a group of clinical entities having non-specific etiology with the common characteristic of acute or chronic inflammatory compromise of the small and large vessels walls, associated with fibrinoid necrosis.

Objectives

To describe the most common inflammatory vascular diseases in a long historical cohort of patients from San Juan de Dios Hospital located in Bogota, Colombia using two different systems and a clinical histopathological correlation format, and to make a comparison between them.

Methods

We reviewed all previously ascertained cases of vasculitis confirmed by biopsy processed between 1953 and 1990, and systematically collected data on all new cases of vasculitis from 1991 to 1997 at the Hospital San Juan de Dios (Bogota – Colombia). The cases were classified in accordance with the Chapel Hill Consensus criteria, and the system proposed by J.T. Lie.

Results

Of 165,556 biopsy tissue specimens obtained during this period from our hospital, 0.18% had vasculitis, perivasculitis or vasculopathy. These included 304 histopathological biopsies from 292 patients. Cutaneous leukocytoclastic vasculitis (64 histological specimens) was the most frequently encountered type of "primary" vasculitis followed by thromboangiitis obliterans (38 specimens), and polyarteritis nodosa (24 specimens). Vasculitis associated with connective tissue diseases (33 specimens) and infection (20 specimens) were the main forms of secondary vasculitis, a category that was omitted from the Chapel Hill consensus report. We found that 65.8% of our histopathological diagnoses could not be classified according to the Chapel Hill classification, and 35.2% could not be classified according to the classification of Lie. Only 8.9% of cases remained unclassified by our system after clinical and histological correlation.

Conclusion

Current vasculitis classification schemes are designed for classification, rather that diagnosis of disease and do not adequately address some common forms of inflammatory vascular diseases, including those of infectious etiology and unusual etiology seen in clinical practice. Based on our clinical experience, we suggest a classification outline which practitioners can use which emphasizes correlation of the clinical picture to the histopathology findings for diagnosis and therapy, which may promote better clinical practice and standardization for clinical trials.

     

Supporting cognition in systems biology analysis: findings on users' processes and design implications

Background

Current usability studies of bioinformatics tools suggest that tools for exploratory analysis support some tasks related to finding relationships of interest but not the deep causal insights necessary for formulating plausible and credible hypotheses. To better understand design requirements for gaining these causal insights in systems biology analyses a longitudinal field study of 15 biomedical researchers was conducted. Researchers interacted with the same protein-protein interaction tools to discover possible disease mechanisms for further experimentation.

Results

Findings reveal patterns in scientists' exploratory and explanatory analysis and reveal that tools positively supported a number of well-structured query and analysis tasks. But for several of scientists' more complex, higher order ways of knowing and reasoning the tools did not offer adequate support. Results show that for a better fit with scientists' cognition for exploratory analysis systems biology tools need to better match scientists' processes for validating, for making a transition from classification to model-based reasoning, and for engaging in causal mental modelling.

Conclusion

As the next great frontier in bioinformatics usability, tool designs for exploratory systems biology analysis need to move beyond the successes already achieved in supporting formulaic query and analysis tasks and now reduce current mismatches with several of scientists' higher order analytical practices. The implications of results for tool designs are discussed.

     

Prevalence of the pathogenic chytrid fungus, Batrachochytrium dendrobatidis, in an endangered population of northern leopard frogs, Rana pipiens

Background

Emerging infectious diseases threaten naïve host populations with extinction. Chytridiomycosis, an emerging infectious disease of amphibians, is caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd) and has been linked to global declines in amphibians.

Results

We monitored the prevalence of Bd for four years in the Northern leopard frog, Rana pipiens, which is critically imperiled in British Columbia (BC), Canada. The prevalence of Bd initially increased and then remained constant over the last three years of the study. Young of the year emerging from breeding ponds in summer were rarely infected with Bd. Some individuals cleared their Bd infections and the return rate between infected and uninfected individuals was not significantly different.

Conclusions

The BC population of R. pipiens appears to have evolved a level of resistance that allows it to co-exist with Bd. However, this small population of R. pipiens remains vulnerable to extinction.

     

Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear production and tear stability and reduced immunopathology in rabbits with induced autoimmune dacryoadenitis

Background

The most common cause of ocular morbidity in developed countries is dry eye, many cases of which are due to lacrimal insufficiency. Dry eye affects approximately 10 million in the United States., most of whom are women. In the U.S. alone, an estimated 2 million Sjögren's syndrome patients have dysfunctional lacrimal glands and severe dry eye, and there is no satisfactory treatment. These patients would benefit if their lacrimal tissue function could be restored.

Methods

The effect of adenovirus-mediated transfer of tumor necrosis factor (TNF)-α inhibitor gene on induced autoimmune dacryoadenitis was evaluated in a rabbit model. Soluble transgene protein was detected in tears by ELISA for 7 days following transduction.

Results

Two weeks after induction of disease with activated lymphocytes, tear production, as determined by Schirmer testing, was reduced by about 40%, while tear film stability, as measured by tear breakup time (BUT), declined by 43%. Adenovirus-mediated gene therapy using AdTNFRp55-Ig given 2 weeks after disease induction, resulted in the return of tear production to normal levels by week 4. In the treated disease group, tear BUT improved significantly by week 4. Rose bengal scores, an indicator of corneal surface defects, increased after disease induction and declined after gene therapy. In the lacrimal gland, the CD4 to CD8 T cell ratio was 4:1 in the disease group compared to 1:2 in the treated group. Infiltration of T cells and CD18+ cells was reduced approximately 50% after gene therapy.

Conclusion

We concluded that therapeutic levels of soluble TNF inhibitor were achieved in the lacrimal gland and on the corneal surface. Anti-inflammatory cytokine gene expression might offer a potential therapeutic modality for the treatment of autoimmune dacryoadenitis, once suitable vectors become available.

     

Cost of resistance to trematodes in freshwater snail populations with low clonal diversity

Background

The persistence of high genetic variability in natural populations garners considerable interest among ecologists and evolutionary biologists. One proposed hypothesis for the maintenance of high levels of genetic diversity relies on frequency-dependent selection imposed by parasites on host populations (Red Queen hypothesis). A complementary hypothesis suggests that a trade-off between fitness costs associated with tolerance to stress factors and fitness costs associated with resistance to parasites is responsible for the maintenance of host genetic diversity.

Results

The present study investigated whether host resistance to parasites is traded off with tolerance to environmental stress factors (high/low temperatures, high salinity), by comparing populations of the freshwater snail Melanoides tuberculata with low vs. high clonal diversity. Since polyclonal populations were found to be more parasitized than populations with low clonal diversity, we expected them to be tolerant to environmental stress factors. We found that clonal diversity explained most of the variation in snail survival under high temperature, thereby suggesting that tolerance to high temperatures of clonally diverse populations is higher than that of populations with low clonal diversity.

Conclusions

Our results suggest that resistance to parasites may come at a cost of reduced tolerance to certain environmental stress factors.