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1.

Background

High-throughput technologies like functional screens and gene expression analysis produce extended lists of candidate genes. Gene-Set Enrichment Analysis is a commonly used and well established technique to test for the statistically significant over-representation of particular pathways. A shortcoming of this method is however, that most genes that are investigated in the experiments have very sparse functional or pathway annotation and therefore cannot be the target of such an analysis. The approach presented here aims to assign lists of genes with limited annotation to previously described functional gene collections or pathways. This works by comparing InterPro domain signatures of the candidate gene lists with domain signatures of gene sets derived from known classifications, e.g. KEGG pathways.

Results

In order to validate our approach, we designed a simulation study. Based on all pathways available in the KEGG database, we create test gene lists by randomly selecting pathway genes, removing these genes from the known pathways and adding variable amounts of noise in the form of genes not annotated to the pathway. We show that we can recover pathway memberships based on the simulated gene lists with high accuracy. We further demonstrate the applicability of our approach on a biological example.

Conclusion

Results based on simulation and data analysis show that domain based pathway enrichment analysis is a very sensitive method to test for enrichment of pathways in sparsely annotated lists of genes. An R based software package domainsignatures, to routinely perform this analysis on the results of high-throughput screening, is available via Bioconductor.  相似文献   

2.

Background

The large and constantly evolving HIV-1 pandemic has led to an increasingly complex diversity. Because of some taxonomic difficulties among the most diverse HIV-1 subtypes, and taking advantage of the large amount of sequence data generated in the recent years, we investigated novel lineage patterns among the main HIV-1 subtypes.

Results

All HIV full-length genomes available in public databases were analysed (n?=?2017). Maximum likelihood phylogenies and pairwise genetic distance were obtained. Clustering patterns and mean distributions of genetic distances were compared within and across the current groups, subtypes and sub-subtypes of HIV-1 to detect and analyse any divergent lineages within previously defined HIV lineages. The level of genetic similarity observed between most HIV clades was deeply consistent with the current classification. However, both subtypes A and D showed evidence of further intra-subtype diversification not fully described by the nomenclature system at the time and could be divided into several distinct sub-subtypes.

Conclusions

With this work, we propose an updated nomenclature of sub-types A and D better reflecting their current genetic diversity and evolutionary patterns. Allowing a more accurate nomenclature and classification system is a necessary step for easier subtyping of HIV strains and a better detection or follow-up of viral epidemiology shifts.
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Background

The majority of experimentally verified molecular interaction and biological pathway data are present in the unstructured text of biomedical journal articles where they are inaccessible to computational methods. The Biomolecular interaction network database (BIND) seeks to capture these data in a machine-readable format. We hypothesized that the formidable task-size of backfilling the database could be reduced by using Support Vector Machine technology to first locate interaction information in the literature. We present an information extraction system that was designed to locate protein-protein interaction data in the literature and present these data to curators and the public for review and entry into BIND.

Results

Cross-validation estimated the support vector machine's test-set precision, accuracy and recall for classifying abstracts describing interaction information was 92%, 90% and 92% respectively. We estimated that the system would be able to recall up to 60% of all non-high throughput interactions present in another yeast-protein interaction database. Finally, this system was applied to a real-world curation problem and its use was found to reduce the task duration by 70% thus saving 176 days.

Conclusions

Machine learning methods are useful as tools to direct interaction and pathway database back-filling; however, this potential can only be realized if these techniques are coupled with human review and entry into a factual database such as BIND. The PreBIND system described here is available to the public at http://bind.ca. Current capabilities allow searching for human, mouse and yeast protein-interaction information.  相似文献   

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Background

Interest in ethnomedicine has grown in the last decades, with much research focusing on how local medicinal knowledge can contribute to Western medicine. Researchers have emphasized the divide between practices used by local medical practitioners and Western doctors. However, researchers have also suggested that merging concepts and practices from local medicinal knowledge and Western science have the potential to improve public health and support medical independence of local people. In this article we study the relations between local and Western medicinal knowledge within a native Amazonian population, the Tsimane'.

Methods

We used the following methods: 1) participant observation and semi-structured interviews to gather background information, 2) free-listing and pile-sorting to assess whether Tsimane' integrate local medicinal knowledge and Western medicine at the conceptual level, 3) surveys to assess to what extent Tsimane' combine local medicinal knowledge with Western medicine in actual treatments, and 4) a participatory workshop to assess the willingness of Tsimane' and Western medical specialists to cooperate with each other.

Results

We found that when asked about medical treatments, Tsimane' do not include Western treatments in their lists, however on their daily practices, Tsimane' do use Western treatments in combination with ethnomedical treatments. We also found that Tsimane' healers and Western doctors express willingness to cooperate with each other and to promote synergy between local and Western medical systems.

Conclusion

Our findings contrast with previous research emphasizing the divide between local medical practitioners and Western doctors and suggests that cooperation between both health systems might be possible.  相似文献   

11.

Purpose

Roots are inhabited by a broad range of fungi, including pathogens and mycorrhizal fungi, with functional traits related to plant health and nutrition. Management of these fungi in agroecosystems requires profound knowledge about their ecology. The main objective of this study was to examine succession patterns of root-associated fungi in pea during a full plant growth cycle.

Methods

Plants were grown in pots with field soil in a growth chamber under controlled conditions. Fungal communities in pea roots were analyzed at different plant growth stages including the vegetative growth, flowering and senescence, using 454 pyrosequencing.

Results

One hundred and twenty one non-singleton operational taxonomic units (OTUs) representing fungal species were detected. Pathogenic and arbuscular mycorrhizal fungi dominated during the vegetative growth stage, whereas saprotrophic fungi dominated during plant senescence.

Conclusions

In conclusion, the results from the present study demonstrated highly diverse fungal communities in pea roots with clear succession patterns related to fungal traits.  相似文献   

12.

Background

The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture.

Methods

The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed.

Results

20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture.

Conclusion

The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.  相似文献   

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Background

While scoliosis has, for a long time, been defined as a three-dimensional (3D) deformity, morphological classifications are confined to the two dimensions of radiographic assessments. The actually existing 3-D classification proposals have been developed in research laboratories and appear difficult to be understood by clinicians.

Aim of the study

The aim of this study was to use the results of a 3D evaluation to obtain a simple and clinically oriented morphological classification (3-DEMO) that might make it possible to distinguish among different populations of scoliotic patients.

Method

We used a large database of evaluations obtained through an optoelectronic system (AUSCAN) that gives a 3D reconstruction of the spine. The horizontal view was used, with a spinal reference system (Top View). An expert clinician evaluated the morphological reconstruction of 149 pathological spines in order to find parameters that could be used for classificatory ends. These were verified in a mathematical way and through computer simulations: some parameters had to be excluded. Pathological data were compared with those of 20 normal volunteers.

Results

We found three classificatory parameters, which are fully described and discussed in this paper: Direction, the angle between spinal pathological and normal AP axis; Shift, the co-ordinates of the barycentre of the Top View; Phase, the parameter describing the spatial evolution of the curve. Using these parameters it was possible to distinguish normal and pathological spines, to classify our population and to differentiate scoliotic patients with identical AP classification but different 3D behaviors.

Conclusion

The 3-DEMO classification offers a new and simple way of viewing the spine through an auxiliary plane using a spinal reference system. Further studies are currently under way to compare this new system with the existing 3-D classifications, to obtain it using everyday clinical and x-rays data, and to develop a triage for clinical use.  相似文献   

15.

Background

Implementation of evidence-based mental health assessment and intervention in community public health practice is a high priority for multiple stakeholders. Academic-community partnerships can assist in the implementation of efficacious treatments in community settings; yet, little is known about the processes by which these collaborations are developed. In this paper, we discuss our application of community-based participatory research (CBPR) approach to implementation, and we present six lessons we have learned from the establishment of an academic-community partnership.

Methods

With older adults with psychosis as a focus, we have developed a partnership between a university research center and a public mental health service system based on CBPR. The long-term goal of the partnership is to collaboratively establish an evidence-based implementation network that is sustainable within the public mental healthcare system.

Results

In building a sustainable partnership, we found that the following lessons were instrumental: changing attitudes; sharing staff; expecting obstacles and formalizing solutions; monitoring and evaluating; adapting and adjusting; and taking advantage of emerging opportunities. Some of these lessons were previously known principles that were modified as the result of the CBPR process, while some lessons derived directly from the interactive process of forming the partnership.

Conclusion

The process of forming of academic-public partnerships is challenging and time consuming, yet crucial for the development and implementation of state-of-the-art approaches to assessment and interventions to improve the functioning and quality of life for persons with serious mental illnesses. These partnerships provide necessary organizational support to facilitate the implementation of clinical research findings in community practice benefiting consumers, researchers, and providers.  相似文献   

16.

Background

We aimed to make individual patient data from the International Stroke Trial (IST), one of the largest randomised trials ever conducted in acute stroke, available for public use, to facilitate the planning of future trials and to permit additional secondary analyses.

Methods

For each randomised patient, we have extracted data on the variables assessed at randomisation, at the early outcome point (14-days after randomisation or prior discharge) and at 6-months and provide them as an analysable database.

Results

The IST dataset includes data on 19 435 patients with acute stroke, with 99% complete follow-up. Over 26.4% patients were aged over 80 years at study entry. Background stroke care was limited and none of the patients received thrombolytic therapy.

Conclusions

The IST dataset provides a source of primary data which could be used for planning further trials, for sample size calculations and for novel secondary analyses. Given the age distribution and nature of the background treatment given, the data may be of value in planning trials in older patients and in resource-poor settings.  相似文献   

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Background

There is an extensive body of literature on health system quality reporting that has yet to be characterized. Scoping is a novel methodology for systematically assessing the breadth of a body of literature in a particular research area. Our objectives were to showcase the scoping review methodology in the review of health system quality reporting, and to report on the extent of the literature in this area.

Methods

A scoping review was performed based on the York methodology outlined by Arksey and O'Malley from the University of York, United Kingdom. We searched 14 peer reviewed and grey literature databases limiting the search to English language and non-English language articles with English abstracts published between 1980 and June 2006 with an update to November 2008. We also searched specific websites, reference lists, and key journals for relevant material and solicited input from key stakeholders. Inclusion/exclusion criteria were applied to select relevant material and qualitative information was charted from the selected literature.

Results

A total of 10,102 articles were identified from searching the literature databases, 821 were deemed relevant to our scoping review. An additional 401 were identified from updates, website searching, references lists, key journals, and stakeholder suggestions for a total of 1,222 included articles. These were categorized and catalogued according to the inclusion criteria, and further subcategories were identified through the charting process. Topic areas represented by this review included the effectiveness of health system report cards (n = 194 articles), methodological issues in their development (n = 815 articles), stakeholder views on report cards (n = 144 articles), and ethical considerations around their development (n = 69 articles).

Conclusions

The scoping review methodology has permitted us to characterize and catalogue the extensive body of literature pertaining to health system report cards. The resulting literature repository that our review has created can be of use to researchers and health system stakeholders interested in the topic of health system quality measurement and reporting.  相似文献   

19.

Key message

ISSR characterization of Chukrasia populations from the natural range revealed two distinct groups of populations consonant with morphological differentiation. Results suggest the current taxonomic classification of the genus should be reviewed.

Abstract

There are different views as to whether the genus Chukrasia (Meliaceae) consists of one species, C. tabularis, or two species C. tabularis and C. velutina. Despite a clear pattern of variation in many morphological characteristics such as leaves and bark, some authors regard the latter merely an ecotype of the former in seasonal forest. In the present study, we used ISSR markers to determine the genetic diversity and population structure among 23 Chukrasia subpopulations from across the natural range in Asia. Molecular analysis clearly differentiated two distinct groups of subpopulations, corresponding to the putative species, as well as well-defined subpopulations corresponding to geographic regions within the two groups. The molecular results are in concordance with morphological differentiation and corresponded to the two recognized taxa. The present study suggests that current taxonomic classification of the genus Chukrasia should be reviewed.  相似文献   

20.

Background

BLAST is a commonly-used software package for comparing a query sequence to a database of known sequences; in this study, we focus on protein sequences. Position-specific-iterated BLAST (PSI-BLAST) iteratively searches a protein sequence database, using the matches in round i to construct a position-specific score matrix (PSSM) for searching the database in round i?+?1. Biegert and S?ding developed Context-sensitive BLAST (CS-BLAST), which combines information from searching the sequence database with information derived from a library of short protein profiles to achieve better homology detection than PSI-BLAST, which builds its PSSMs from scratch.

Results

We describe a new method, called domain enhanced lookup time accelerated BLAST (DELTA-BLAST), which searches a database of pre-constructed PSSMs before searching a protein-sequence database, to yield better homology detection. For its PSSMs, DELTA-BLAST employs a subset of NCBI??s Conserved Domain Database (CDD). On a test set derived from ASTRAL, with one round of searching, DELTA-BLAST achieves a ROC5000 of 0.270 vs. 0.116 for CS-BLAST. The performance advantage diminishes in iterated searches, but DELTA-BLAST continues to achieve better ROC scores than CS-BLAST.

Conclusions

DELTA-BLAST is a useful program for the detection of remote protein homologs. It is available under the ??Protein BLAST?? link at http://blast.ncbi.nlm.nih.gov.

Reviewers

This article was reviewed by Arcady Mushegian, Nick V. Grishin, and Frank Eisenhaber.  相似文献   

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