Catalogue of Somatic Mutations in Cancer (COSMIC) (http://www.sanger.ac.uk/cosmic) is a publicly available resource providing information on somatic mutations implicated in human cancer. Release v51 (January 2011) includes data from just over 19 000 genes, 161 787 coding mutations and 5573 gene fusions, described in more than 577 000 tumour samples. COSMICMart (COSMIC BioMart) provides a flexible way to mine these data and combine somatic mutations with other biological relevant data sets. This article describes the data available in COSMIC along with examples of how to successfully mine and integrate data sets using COSMICMart.
Database URL: http://www.sanger.ac.uk/genetics/CGP/cosmic/biomart/martview/
The catalogue of Somatic Mutations in Cancer (COSMIC) (http://www.sanger.ac.uk/cosmic/) is the largest public resource for information on somatically acquired mutations in human cancer and is available freely without restrictions. Currently (v43, August 2009), COSMIC contains details of 1.5-million experiments performed through 13 423 genes in almost 370 000 tumours, describing over 90 000 individual mutations. Data are gathered from two sources, publications in the scientific literature, (v43 contains 7797 curated articles) and the full output of the genome-wide screens from the Cancer Genome Project (CGP) at the Sanger Institute, UK. Most of the world’s literature on point mutations in human cancer has now been curated into COSMIC and while this is continually updated, a greater emphasis on curating fusion gene mutations is driving the expansion of this information; over 2700 fusion gene mutations are now described. Whole-genome sequencing screens are now identifying large numbers of genomic rearrangements in cancer and COSMIC is now displaying details of these analyses also. Examination of COSMIC’s data is primarily web-driven, focused on providing mutation range and frequency statistics based upon a choice of gene and/or cancer phenotype. Graphical views provide easily interpretable summaries of large quantities of data, and export functions can provide precise details of user-selected data.
COSMIC is currently the most comprehensive global resource for information on somatic mutations in human cancer, combining curation of the scientific literature with tumor resequencing data from the Cancer Genome Project at the Sanger Institute, U.K. Almost 4800 genes and 250000 tumors have been examined, resulting in over 50000 mutations available for investigation. This information can be accessed in a number of ways, the most convenient being the Web-based system which allows detailed data mining, presenting the results in easily interpretable formats. This unit describes the graphical system in detail, elaborating an example walkthrough and the many ways that the resulting information can be thoroughly investigated by combining data, respecializing the query, or viewing the results in different ways. Alternate protocols overview the available precompiled data files available for download.
COSMIC; cancer; somatic; mutation; database
COSMIC (http://www.sanger.ac.uk/cosmic) curates comprehensive information on somatic mutations in human cancer. Release v48 (July 2010) describes over 136 000 coding mutations in almost 542 000 tumour samples; of the 18 490 genes documented, 4803 (26%) have one or more mutations. Full scientific literature curations are available on 83 major cancer genes and 49 fusion gene pairs (19 new cancer genes and 30 new fusion pairs this year) and this number is continually increasing. Key amongst these is TP53, now available through a collaboration with the IARC p53 database. In addition to data from the Cancer Genome Project (CGP) at the Sanger Institute, UK, and The Cancer Genome Atlas project (TCGA), large systematic screens are also now curated. Major website upgrades now make these data much more mineable, with many new selection filters and graphics. A Biomart is now available allowing more automated data mining and integration with other biological databases. Annotation of genomic features has become a significant focus; COSMIC has begun curating full-genome resequencing experiments, developing new web pages, export formats and graphics styles. With all genomic information recently updated to GRCh37, COSMIC integrates many diverse types of mutation information and is making much closer links with Ensembl and other data resources.
The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines.
somatic; mutation; database; website
Objectives: US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots.
Methods: Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments’ block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty.
Results: Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (Ptrend < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman’s r = 0.61–0.69).
Conclusions: The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies.
circadian disruption; cosmic radiation; exposure assessment; flight crew; pilots
With the advent of whole-genome analysis for profiling tumor tissue, a pressing need has emerged for principled methods of organizing the large amounts of resulting genomic information. We propose the concept of multiplicity measures on cancer and gene networks to organize the information in a clinically meaningful manner. Multiplicity applied in this context extends Fearon and Vogelstein's multi-hit genetic model of colorectal carcinoma across multiple cancers.
Using the Catalogue of Somatic Mutations in Cancer (COSMIC), we construct networks of interacting cancers and genes. Multiplicity is calculated by evaluating the number of cancers and genes linked by the measurement of a somatic mutation. The Kamada-Kawai algorithm is used to find a two-dimensional minimum energy solution with multiplicity as an input similarity measure. Cancers and genes are positioned in two dimensions according to this similarity. A third dimension is added to the network by assigning a maximal multiplicity to each cancer or gene. Hierarchical clustering within this three-dimensional network is used to identify similar clusters in somatic mutation patterns across cancer types.
The clustering of genes in a three-dimensional network reveals a similarity in acquired mutations across different cancer types. Surprisingly, the clusters separate known causal mutations. The multiplicity clustering technique identifies a set of causal genes with an area under the ROC curve of 0.84 versus 0.57 when clustering on gene mutation rate alone. The cluster multiplicity value and number of causal genes are positively correlated via Spearman's Rank Order correlation (rs(8) = 0.894, Spearman's t = 17.48, p < 0.05). A clustering analysis of cancer types segregates different types of cancer. All blood tumors cluster together, and the cluster multiplicity values differ significantly (Kruskal-Wallis, H = 16.98, df = 2, p < 0.05).
We demonstrate the principle of multiplicity for organizing somatic mutations and cancers in clinically relevant clusters. These clusters of cancers and mutations provide representations that identify segregations of cancer and genes driving cancer progression.
The massive use of Next-Generation Sequencing (NGS) technologies is uncovering an unexpected amount of variability. The functional characterization of such variability, particularly in the most common form of variation found, the Single Nucleotide Variants (SNVs), has become a priority that needs to be addressed in a systematic way. VARIANT (VARIant ANalyis Tool) reports information on the variants found that include consequence type and annotations taken from different databases and repositories (SNPs and variants from dbSNP and 1000 genomes, and disease-related variants from the Genome-Wide Association Study (GWAS) catalog, Online Mendelian Inheritance in Man (OMIM), Catalog of Somatic Mutations in Cancer (COSMIC) mutations, etc). VARIANT also produces a rich variety of annotations that include information on the regulatory (transcription factor or miRNA-binding sites, etc.) or structural roles, or on the selective pressures on the sites affected by the variation. This information allows extending the conventional reports beyond the coding regions and expands the knowledge on the contribution of non-coding or synonymous variants to the phenotype studied. Contrarily to other tools, VARIANT uses a remote database and operates through efficient RESTful Web Services that optimize search and transaction operations. In this way, local problems of installation, update or disk size limitations are overcome without the need of sacrifice speed (thousands of variants are processed per minute). VARIANT is available at: http://variant.bioinfo.cipf.es.
As large-scale re-sequencing of genomes reveals many protein mutations, especially in human cancer tissues, prediction of their likely functional impact becomes important practical goal. Here, we introduce a new functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns. The information in these patterns is derived from aligned families and sub-families of sequence homologs within and between species using combinatorial entropy formalism. The score performs well on a large set of human protein mutations in separating disease-associated variants (∼19 200), assumed to be strongly functional, from common polymorphisms (∼35 600), assumed to be weakly functional (area under the receiver operating characteristic curve of ∼0.86). In cancer, using recurrence, multiplicity and annotation for ∼10 000 mutations in the COSMIC database, the method does well in assigning higher scores to more likely functional mutations (‘drivers’). To guide experimental prioritization, we report a list of about 1000 top human cancer genes frequently mutated in one or more cancer types ranked by likely functional impact; and, an additional 1000 candidate cancer genes with rare but likely functional mutations. In addition, we estimate that at least 5% of cancer-relevant mutations involve switch of function, rather than simply loss or gain of function.
Background: Earlier studies have found increased breast cancer risk among female cabin crew. This has been suggested to reflect lifestyle factors (for example, age at first birth), other confounding factors (for example, age at menarche), or occupational factors such as exposure to cosmic radiation and circadian rhythm alterations due to repeated jet lag.
Aims: To assess the contribution of occupational versus lifestyle and other factors to breast cancer risk among cabin attendants in Finland.
Methods: A standardised self-administered questionnaire on demographic, occupational, and lifestyle factors was given to 1041 cabin attendants. A total of 27 breast cancer cases and 517 non-cases completed the questionnaire. Breast cancer diagnoses were confirmed through the Finnish Cancer Registry. Exposure to cosmic radiation was estimated based on self-reported flight history and timetables. A conditional logistic regression model was used for analysis.
Results: In the univariate analysis, family history of breast cancer (OR = 2.67, 95% CI: 1.00 to 7.08) was the strongest determinant of breast cancer. Of occupational exposures, sleep rhythm disruptions (OR = 1.72, 95% CI: 0.70 to 4.27) were positively related and disruption of menstrual cycles (OR = 0.71, 95% CI: 0.26 to 1.96) negatively related to breast cancer. However, both associations were statistically non-significant. Cumulative radiation dose (OR = 0.99, 95% CI: 0.83 to 1.19) showed no effect on breast cancer.
Conclusions: Results suggest that breast cancer risk among Finnish cabin attendants is related to well established risk factors of breast cancer, such as family history of breast cancer. There was no clear evidence that the three occupational factors studied affected breast cancer risk among Finnish flight attendants.
The richest uranium ore bodies ever discovered (Cigar Lake and McArthur River) are presently under development in northeastern Saskatchewan. This subarctic region is also home to several operating uranium mines and aboriginal communities, partly dependent upon caribou for subsistence. Because of concerns over mining impacts and the efficient transfer of airborne radionuclides through the lichen-caribou-human food chain, radionuclides were analyzed in tissues from 18 barren-ground caribou (Rangifer tarandus groenlandicus). Radionuclides included uranium (U), radium (226Ra), lead (210Pb), and polonium (210Po) from the uranium decay series; the fission product (137Cs) from fallout; and naturally occurring potassium (40K). Natural background radiation doses average 2-4 mSv/year from cosmic rays, external gamma rays, radon inhalation, and ingestion of food items. The ingestion of 210Po and 137Cs when caribou are consumed adds to these background doses. The dose increment was 0.85 mSv/year for adults who consumed 100 g of caribou meat per day and up to 1.7 mSv/year if one liver and 10 kidneys per year were also consumed. We discuss the cancer risk from these doses. Concentration ratios (CRs), relating caribou tissues to lichens or rumen (stomach) contents, were calculated to estimate food chain transfer. The CRs for caribou muscle ranged from 1 to 16% for U, 6 to 25% for 226Ra, 1 to 2% for 210Pb, 6 to 26% for 210Po, 260 to 370% for 137Cs, and 76 to 130% for 40K, with 137Cs biomagnifying by a factor of 3-4. These CRs are useful in predicting caribou meat concentrations from the lichens, measured in monitoring programs, for the future evaluation of uranium mining impacts on this critical food chain.
To assess the incidence of cancer among male airline pilots in the Nordic countries, with special reference to risk related to cosmic radiation.
Retrospective cohort study, with follow up of cancer incidence through the national cancer registries.
Denmark, Finland, Iceland, Norway, and Sweden.
10 032 male airline pilots, with an average follow up of 17 years.
Main outcome measures
Standardised incidence ratios, with expected numbers based on national cancer incidence rates; dose-response analysis using Poisson regression.
466 cases of cancer were diagnosed compared with 456 expected. The only significantly increased standardised incidence ratios were for skin cancer: melanoma 2.3 (95% confidence interval 1.7 to 3.0), non-melanoma 2.1 (1.7 to 2.8), basal cell carcinoma 2.5 (1.9 to 3.2). The relative risk of skin cancers increased with the estimated radiation dose. The relative risk of prostate cancer increased with increasing number of flight hours in long distance aircraft.
This study does not indicate a marked increase in cancer risk attributable to cosmic radiation, although some influence of cosmic radiation on skin cancer cannot be entirely excluded. The suggestion of an association between number of long distance flights (possibly related to circadian hormonal disturbances) and prostate cancer needs to be confirmed.
What is already known on this topicAirline pilots are occupationally exposed to cosmic radiation and other potentially carcinogenic elementsIn the studies published so far, dose-response patterns have not been characterisedWhat this study addsNo marked risk of cancer attributable to cosmic radiation is observed in airline pilotsA threefold excess of skin cancers is seen among pilots with longer careers, but the influence of recreational exposure to ultraviolet light cannot be quantifiedA slight increase in risk of prostate cancer with increasing number of long haul flights suggests a need for more studies on the effects of circadian hormonal disturbances
Ionizing radiation long has been recognized as a cause of cancer. Among environmental cancer risks, radiation is unique in the variety of organs and tissues that it can affect. Numerous epidemiological studies with good dosimetry provide the basis for cancer risk estimation, including quantitative information derived from observed dose-response relationships. The amount of cancer attributable to ionizing radiation is difficult to estimate, but numbers such as 1 to 3% have been suggested. Some radiation-induced cancers attributable to naturally occurring exposures, such as cosmic and terrestrial radiation, are not preventable. The major natural radiation exposure, radon, can often be reduced, especially in the home, but not entirely eliminated. Medical use of radiation constitutes the other main category of exposure; because of the importance of its benefits to one's health, the appropriate prevention strategy is to simply work to minimize exposures.
Carcinogenesis induced by space radiation is considered a major risk factor in manned interplanetary and other extended missions. The models presently used to estimate the risk for cancer induction following deep space radiation exposure are based on data from A-bomb survivor cohorts and do not account for important biological differences existing between high-linear energy transfer (LET) and low-LET-induced DNA damage. High-energy and charge (HZE) radiation, the main component of galactic cosmic rays (CGR), causes highly complex DNA damage compared to low-LET radiation, which may lead to increased frequency of chromosomal rearrangements, and contribute to carcinogenic risk in astronauts. Gastrointestinal (GI) tumors are frequent in the United States, and colorectal cancer (CRC) is the third most common cancer accounting for 10% of all cancer deaths. On the basis of the aforementioned epidemiological observations and the frequency of spontaneous precancerous GI lesions in the general population, even a modest increase in incidence by space radiation exposure could have a significant effect on health risk estimates for future manned space flights. Ground-based research is necessary to reduce the uncertainties associated with projected cancer risk estimates and to gain insights into molecular mechanisms involved in space radiation-induced carcinogenesis. We investigated in vivo differential effects of γ-rays and HZE ions on intestinal tumorigenesis using two different murine models, ApcMin/+ and Apc1638 N/+. We showed that γ- and/or HZE exposure significantly enhances development and progression of intestinal tumors in a mutant-line-specific manner, and identified suitable models for in vivo studies of space radiation–induced intestinal tumorigenesis.
Apc; intestinal tumorigenesis; space radiation; risk estimates
This article reports measurements of household levels of gamma and cosmic rays at the addresses of children with cancer at the time of diagnosis and six months before, and of similar data at the addresses of control children. There is no indication of increased risk with increasing dose rates either in matched or unmatched analyses, with or without adjustment for deprivation. Sub-division by diagnostic group did not reveal any association with any specific types of malignancy. Studies of the relationship between household gamma rays and radon concentration show no evidence of any interactions.
British Journal of Cancer (2002) 86, 1727–1731. doi:10.1038/sj.bjc.6600277 www.bjcancer.com
© 2002 Cancer Research UK
childhood cancer; gamma dose rate; radon interactions; acute lymphoblastic leukaemia; non-Hodgkin's lymphoma; central nervous system tumours
Cancer-associated mutations in cancer genes constitute a diverse set of mutations associated with the disease. To gain insight into features of the set, substitution, deletion and insertion mutations were analysed at the nucleotide level, from the COSMIC database. The most frequent substitutions were c→t, g→a, g→t, and the most frequent codon changes were to termination codons. Deletions more than insertions, FS (frameshift) indels more than I-F (in-frame) ones, and single-nucleotide indels, were frequent. FS indels cause loss of significant fractions of proteins. The 5′-cut in FS deletions, and 5′-ligation in FS insertions, often occur between pairs of identical bases. Interestingly, the cut-site and 3′-ligation in insertions, and 3′-cut and join-pair in deletions, were each found to be the same significantly often (p < 0.001). It is suggested that these features aid the incorporation of indel mutations. Tumor suppressors undergo larger numbers of mutations, especially disruptive ones, over the entire protein length, to inactivate two alleles. Proto-oncogenes undergo fewer, less-disruptive mutations, in selected protein regions, to activate a single allele. Finally, catalogues, in ranked order, of genes mutated in each cancer, and cancers in which each gene is mutated, were created. The study highlights the nucleotide level preferences and disruptive nature of cancer mutations.
Humans are exposed to ionizing radiation (IR) under various circumstances, e.g. cosmic radiation, diagnostic X-rays and radiotherapy for cancer. It has been shown that IR can impair spermatogenesis and can cause mutations in germ cells. However, the mutagenic responses of germ cells exposed to IR at different stages of testicular maturation have not been examined by directly assessing the mutant frequency in defined spermatogenic cell types. This study was performed to address whether preadult exposure to IR can increase mutations in adult germ cells that could in turn have a major impact on adult reproductive function and the health of ensuing offspring. Male Lac I transgenic mice were irradiated with a single dose of 2.5 Gy of γ-ray at different ages before adulthood, reflecting different stages of testicular maturation, and then mutant frequency (MF) was determined directly in spermatogenic cell types emanating from the irradiated precursor cells. The results showed that (1) preadult exposure to IR did not significantly increase MF in adult epididymal spermatozoa; (2) spermatogenic stages immediately following the irradiated stage(s) displayed an elevated mutant frequency, but (3) the mutant frequency was restored to unirradiated levels in later stages of spermatogenesis. These findings provide evidence that there is a mechanism(s) to prevent spermatogenic cells with elevated mutant frequencies from progressing through spermatogenesis.
ionizing radiation; mutagenesis; spermatogenic cells; Lac I mouse
The reversible phosphorylation of serine, threonine and tyrosine hydroxyl groups is an especially prominent form of post-translational modification (PTM) of proteins. It plays critical roles in the regulation of diverse processes, and mutations that directly or indirectly affect these phosphorylation events have been associated with many cancers and other pathologies. Here, we describe the development of a new BioMart tool that gathers data from three different biological resources to provide the user with an integrated view of phosphorylation events associated with a human protein of interest, the complexes of which the protein (modified or not) is a part, the reactions in which the protein and its complexes participate and the somatic mutations that might be expected to perturb those functions. The three resources used are the Reactome, PRIDE and COSMIC databases. The Reactome knowledgebase contains annotations of phosphorylated human proteins linked to the reactions in which they are phosphorylated and dephosphorylated, to the complexes of which they are parts and to the reactions in which the phosphorylated proteins participate as substrates, catalysts and regulators. The PRIDE database holds extensive mass spectrometry data from which protein phosphorylation patterns can be inferred, and the COSMIC database holds records of somatic mutations found in human cancer cells. This tool supports both flexible, user-specified queries and standard (‘canned’) queries to retrieve frequently used combinations of data for user-specified proteins and reactions. We demonstrate using the Wnt signaling pathway and the human c-SRC protein how the tool can be used to place somatic mutation data into a functional perspective by changing critical residues involved in pathway modulation, and where available, check for mass spectrometry evidence in PRIDE supporting identification of the critical residue.
Database URL: http://www.reactome.org/cgi-bin/mart
Space exploration is associated with exposure to 1–3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol (Δ5 androsten-3β, 17β-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET 56Fe26+ exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements (p<0.001). Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase (p<0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties.
androstenediol; bone marrow; high LET radiation; hematopoietic; osteoclastogenesis; radioprotector
Galactic Cosmic Radiation consisting of high-energy, high-charged (HZE) particles poses a significant threat to future astronauts in deep space. Aside from cancer, concerns have been raised about late degenerative risks, including effects on the brain. In this study we examined the effects of 56Fe particle irradiation in an APP/PS1 mouse model of Alzheimer’s disease (AD). We demonstrated 6 months after exposure to 10 and 100 cGy 56Fe radiation at 1 GeV/µ, that APP/PS1 mice show decreased cognitive abilities measured by contextual fear conditioning and novel object recognition tests. Furthermore, in male mice we saw acceleration of Aβ plaque pathology using Congo red and 6E10 staining, which was further confirmed by ELISA measures of Aβ isoforms. Increases were not due to higher levels of amyloid precursor protein (APP) or increased cleavage as measured by levels of the β C-terminal fragment of APP. Additionally, we saw no change in microglial activation levels judging by CD68 and Iba-1 immunoreactivities in and around Aβ plaques or insulin degrading enzyme, which has been shown to degrade Aβ. However, immunohistochemical analysis of ICAM-1 showed evidence of endothelial activation after 100 cGy irradiation in male mice, suggesting possible alterations in Aβ trafficking through the blood brain barrier as a possible cause of plaque increase. Overall, our results show for the first time that HZE particle radiation can increase Aβ plaque pathology in an APP/PS1 mouse model of AD.
The purpose of this paper is a review of a number of studies considering links between life threatening cardiac arrhythmias, sudden cardiac death (SCD) and the level of environmental physical activity factors like geomagnetic activity (GMA) and opposite them cosmic ray and high energy proton flux. This is a part of studies in the field named Clinical Cosmobiology.
Temporal distribution of cardiac arrhythmias and SCD daily and monthly were compared to the level of GMA, space proton flux, cosmic ray activity according to neutron activity (impulse/min) on the earth's surface. The cosmophysical data was obtained from the cosmic science institutions in the USA, Russia and Finland (cosmic ray data, partially).
As it follows from the results of the quoted studies there is an inverse relationship between the frequency of cardiac arrhythmic events and SCD and the level of daily GMA.
Now studies are in progress considering the role of neutron (cosmic ray) activity in the natural history of the mentioned events. According to the various studies, we can presume that the GMA has some protective effect on cardiac arrhythmias and SCD.
sudden cardiac death; cardiac arrhythmia; geomagnetic activity; proton flux; cosmic ray
DNA methylation is an important epigenetic modification of the genome. Abnormal DNA methylation may result in silencing of tumor suppressor genes and is common in a variety of human cancer cells. As more epigenetics research is published electronically, it is desirable to extract relevant information from biological literature. To facilitate epigenetics research, we have developed a database called MeInfoText to provide gene methylation information from text mining.
MeInfoText presents comprehensive association information about gene methylation and cancer, the profile of gene methylation among human cancer types and the gene methylation profile of a specific cancer type, based on association mining from large amounts of literature. In addition, MeInfoText offers integrated protein-protein interaction and biological pathway information collected from the Internet. MeInfoText also provides pathway cluster information regarding to a set of genes which may contribute the development of cancer due to aberrant methylation. The extracted evidence with highlighted keywords and the gene names identified from each methylation-related abstract is also retrieved. The database is now available at .
MeInfoText is a unique database that provides comprehensive gene methylation and cancer association information. It will complement existing DNA methylation information and will be useful in epigenetics research and the prevention of cancer.
Mining gene patterns that are common to multiple genomes is an important biological problem, which can lead us to novel biological insights. When family classification of genes is available, this problem is similar to the pattern mining problem in the data mining community. However, when family classification information is not available, mining gene patterns is a challenging problem. There are several well developed algorithms for predicting gene patterns in a pair of genomes, such as FISH and DAGchainer. These algorithms use the optimization problem formulation which is solved using the dynamic programming technique. Unfortunately, extending these algorithms to multiple genome cases is not trivial due to the rapid increase in time and space complexity.
In this paper, we propose a novel algorithm for mining gene patterns in more than two prokaryote genomes using interchangeable sets. The basic idea is to extend the pattern mining technique from the data mining community to handle the situation where family classification information is not available using interchangeable sets. In an experiment with four newly sequenced genomes (where the gene annotation is unavailable), we show that the gene pattern can capture important biological information. To examine the effectiveness of gene patterns further, we propose an ortholog prediction method based on our gene pattern mining algorithm and compare our method to the bi-directional best hit (BBH) technique in terms of COG orthologous gene classification information. The experiment show that our algorithm achieves a 3% increase in recall compared to BBH without sacrificing the precision of ortholog detection.
The discovered gene patterns can be used for the detecting of ortholog and genes that collaborate for a common biological function.
An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches.
We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER) and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2) is uncovered. We further suggest a likely transcription factor that regulates TACSTD2.
Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype.
A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.