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PubMed2005

BioContrasts: extracting and exploiting protein-protein contrastive relations from biomedical literature.

MOTIVATION: Contrasts are useful conceptual vehicles for learning processes and exploratory research of the unknown. For example, contrastive information between proteins can reveal what similarities, divergences and relations there are of the two proteins, leading to invaluable insights for better understanding about the proteins. Such contrastive information are found to be reported in the biomedical literature. However, there have been no reported attempts in current biomedical text mining work that systematically extract and present such useful contrastive information from the literature for exploitation. RESULTS: Our BioContrasts system extracts protein-protein contrastive information from MEDLINE abstracts and presents the information to biologists in a web-application for exploitation. Contrastive information are identified in the text abstracts with contrastive negation patterns such as 'A but not B'. A total of 799 169 pairs of contrastive expressions were successfully extracted from 2.5 million MEDLINE abstracts. Using grounding of contrastive protein names to Swiss-Prot entries, we were able to produce 41 471 pieces of contrasts between Swiss-Prot protein entries. These contrastive pieces of information are then presented via a user-friendly interactive web portal that can be exploited for applications such as the refinement of biological pathways. AVAILABILITY: BioContrasts can be accessed at http://biocontrasts.i2r.a-star.edu.sg. It is also mirrored at http://biocontrasts.biopathway.org. SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

Artificial Intelligence↗
PubMed2006

Finding the evidence for protein-protein interactions from PubMed abstracts.

MOTIVATION: Protein-protein interactions play critical roles in biological processes, and many biologists try to find or to predict crucial information concerning these interactions. Before verifying interactions in biological laboratory work, validating them from previous research is necessary. Although many efforts have been made to create databases that store verified information in a structured form, much interaction information still remains as unstructured text. As the amount of new publications has increased rapidly, a large amount of research has sought to extract interactions from the text automatically. However, there remain various difficulties associated with the process of applying automatically generated results into manually annotated databases. For interactions that are not found in manually stored databases, researchers attempt to search for abstracts or full papers. RESULTS: As a result of a search for two proteins, PubMed frequently returns hundreds of abstracts. In this paper, a method is introduced that validates protein-protein interactions from PubMed abstracts. A query is generated from two given proteins automatically and abstracts are then collected from PubMed. Following this, target proteins and their synonyms are recognized and their interaction information is extracted from the collection. It was found that 67.37% of the interactions from DIP-PPI corpus were found from the PubMed abstracts and 87.37% of interactions were found from the given full texts. AVAILABILITY: Contact authors.

Abstracting and Indexing↗
PubMed1975

Comprehension and appreciation of humorous material following brain damage.

The effects of brain damage on cognitive and affective status have been assessed separately; however, a dearth of information exists about the interaction of these facets in the brain-damaged patient. Because appreciation of humour involves both cognitive and affective dimensions, an investigation of response to humorous materials should yield information relevant to this issue. In addition, a study of response to humour in aphasic patients can reveal the extent to which appreciation of humour is dependent upon an intact language system. Accordingly a test of humour, in which an individual chose the "funniest" of four cartoons, was administered to a population of brain-damaged and control patients. Ability to detect the most humorous cartoon was impaired in all brain-damaged patients, more in severe than in mild aphasics, but there was no significant difference between patients with left and right hemisphere lesions in their overall performance on the test. A different order of difficulty across items, and a different profile of "mirth" responses to the items did, however, correlate with site of lesion. Right hemisphere patients tended either to laugh throughout or, more frequently, not at all; they often confabulated answers to made impossible inferences; and they performed better on items with captions. Their cognitive reactions appeared "dissociated" from their affective responses. In contrast left hemisphere patients performed better on the captionless items and behaved in a manner which more closely approximated normal subjects in their humorous reactions, their order of item difficulty, and their explanations. All brain-damaged patients found it relatively easier to locate the humorous cartoons when the members of a set differed appreciably from one another. These results provide information about the altered cognitive and affective states of brain-damaged patients, the impairment of cognitive operations in aphasic patients, and the respective "life-spaces" of left and right hemisphere injured patients.

Affect↗
PubMed2000

Archaic lineages in the history of modern humans.

An important question in the ongoing debate on the origin of Homo sapiens is whether modern human populations issued from a single lineage or whether several, independently evolving lineages contributed to their genetic makeup. We analyzed haplotypes composed of 35 polymorphisms from a segment of the dystrophin gene. We find that the bulk of a worldwide sample of 868 chromosomes represents haplotypes shared by different continental groups. The remaining chromosomes carry haplotypes specific for the continents or for local populations. The haplotypes specific for non-Africans can be derived from the most frequent ones through simple recombination or a mutation. In contrast, chromosomes specific for sub-Saharan Africans represent a distinct group, as shown by principal component analysis, maximum likelihood tree, structural comparison, and summary statistics. We propose that African chromosomes descend from at least two lineages that have been evolving separately for a period of time. One of them underwent range expansion colonizing different continents, including Africa, where it mixed with another, local lineage represented today by a large fraction of African-specific haplotypes. Genetic admixture involving archaic lineages appears therefore to have occurred within Africa rather than outside this continent, explaining greater diversity of sub-Saharan populations observed in a variety of genetic systems.

Africa↗
PubMed2001

The Zebrafish Information Network (ZFIN): a resource for genetic, genomic and developmental research.

The Zebrafish Information Network, ZFIN, is a WWW community resource of zebrafish genetic, genomic and developmental research information (http://zfin.org). ZFIN provides an anatomical atlas and dictionary, developmental staging criteria, research methods, pathology information and a link to the ZFIN relational database (http://zfin. org/ZFIN/). The database, built on a relational, object-oriented model, provides integrated information about mutants, genes, genetic markers, mapping panels, publications and contact information for the zebrafish research community. The database is populated with curated published data, user submitted data and large dataset uploads. A broad range of data types including text, images, graphical representations and genetic maps supports the data. ZFIN incorporates links to other genomic resources that provide sequence and ortholog data. Zebrafish nomenclature guidelines and an automated registration mechanism for new names are provided. Extensive usability testing has resulted in an easy to learn and use forms interface with complex searching capabilities.

Animals↗
PubMed2001

Interspecies conservation of gene order and intron-exon structure in a genomic locus of high gene density and complexity in Plasmodium.

A 13.6 kb contig of chromosome 5 of Plasmodium berghei, a rodent malaria parasite, has been sequenced and analysed for its coding potential. Assembly and comparison of this genomic locus with the orthologous locus on chromosome 10 of the human malaria Plasmodium falciparum revealed an unexpectedly high level of conservation of the gene organisation and complexity, only partially predicted by current gene-finder algorithms. Adjacent putative genes, transcribed from complementary strands, overlap in their untranslated regions, introns and exons, resulting in a tight clustering of both regulatory and coding sequences, which is unprecedented for genome organisation of PLASMODIUM: In total, six putative genes were identified, three of which are transcribed in gametocytes, the precursor cells of gametes. At least in the case of two multiple exon genes, alternative splicing and alternative transcription initiation sites contribute to a flexible use of the dense information content of this locus. The data of the small sample presented here indicate the value of a comparative approach for Plasmodium to elucidate structure, organisation and gene content of complex genomic loci and emphasise the need to integrate biological data of all Plasmodium species into the P.falciparum genome database and associated projects such as PlasmodB to further improve their annotation.

Alternative Splicing↗
PubMed1998

B30.2-like domain proteins: update and new insights into a rapidly expanding family of proteins.

The B30.2 domain is a conserved region of around 170 amino acids associated with several different protein domains, including the immunoglobulin folds of butyrophilin and the RING finger domain of ret finger protein. We recently reported several novel members of this family as well as previously undescribed protein families possessing the B30.2 domain. Many proteins have subsequently been found to possess this domain, including pyrin/marenostrin and the midline 1 (MID1) protein. Mutations in the B30.2 domain of pyrin/marenostrin are implicated in familial Mediterranean fever, and partial loss of the B30.2 domain of MID1 is responsible for Opitz G/BBB syndrome, characterized by developmental midline defects. In this study, we scrutinized the available sequence data bases for the identification of novel B30.2 domain proteins using highly sensitive database-searching tools. In addition, we discuss the chromosomal localization of genes in the B30.2 family, since the encoded proteins are likely to be involved in other forms of periodic fever, autoimmune, and genetic diseases.

Amino Acid Sequence↗
PubMed1989

Variances of the average numbers of nucleotide substitutions within and between populations.

Statistical methods for computing the variances of nucleotide diversity within populations and of nucleotide divergence between populations are developed. Both variances are computed by finding the phylogenetic relationships of the DNA sequences studied through the unweighted pair-group method or some other tree-making method. The methods developed are applicable to both DNA sequence and restriction-site map data.

Animals↗
PubMed1999

Mapping variation in brain structure and function: implications for rehabilitation.

The recognition of structural and functional variability of the human brain promoted the development of a system to organize and analyze the rapidly growing body of knowledge acquired among diverse disciplines. The Human Brain Project (HBP) was initiated and has evolved as a means of establishing an information infrastructure through tools related to the emerging science of neuroinformatics. This article will briefly describe the implications that such an endeavor has for the field of traumatic brain injury (TBI) rehabilitation.

Brain↗
PubMed1994

Proposals for a new classification of iridescent viruses.

The need for comparative studies of iridoviruses to elucidate the relationships between them has been well appreciated. Sixteen iridoviruses, including type species from each of the four recognized genera of the Iridoviridae, were compared by restriction endonuclease characterization, hybridization to the major structural protein (MSP) gene of an invertebrate iridescent virus (IV) isolate at various stringencies, PCR amplification of the MSP gene region and by dot-blot hybridization studies. The results broadly supported previous serological studies. The vertebrate iridoviruses, frog virus 3 (genus Ranavirus) and flounder lymphocystivirus (genus Lymphocystivirus), appeared distinct from one another and from the invertebrate isolates. Naming and numbering invertebrate IV isolates according to history and host is no longer useful since IVs infect a number of species. A revised system, involving names based on the geographical origin of the isolate is proposed, in line with other virus families. The large IVs of invertebrates represented by Vero Beach IV (previously IV3 or mosquito IV; genus Chloriridovirus) showed little similarity to any other IVs. Members of the genus Iridovirus, the small invertebrate IVs, fell into three distinct groups of interrelated isolates. The largest group, containing the Plowden (IV1), Tia (IV2), Nelson (IV9, IV10 and IV18), Aberystwyth (IV22), Srinagar (IV24), Fort Collins (IV29) and Stoneville (IV30) iridoviruses, is named the Polyiridovirus complex. The Plowden iridovirus (IV1) is suggested as type species for this complex given the data available on its molecular biology. Based on previously published data, Timaru (IV16 and IV19) and Uitenhage (IV23) iridoviruses are also assigned to this complex. The second but smaller group is named the Oligoiridovirus complex, which includes Dazaifu (IV6) as the type species and contains Ntondwe (IV21 and IV28) on a tentative basis. Riverside IV (IV31) was distinct from both of the other groups, and is proposed as a third complex, Crustaceoiridovirus.

Animals↗
PubMed1996

Partial epileptic seizure with versive movements examined by [99m Tc] HM-PAO brain single photon emission computed tomography: an early post study analyzed by computerized brain atlas methods.

The consecutive steps of a seizure with leftward versive movements of the head and eyes were analyzed after video monitoring and correlated with findings on single photon emission computed tomography (SPECT) using [99m Tc] hexamethyl propylene amine oxime (HM-PAO). Evaluation included reconstruction of subtraction images from the early postictal state, obtained immediately after the video-monitored seizure, and the interictal baseline. Based on normalized perfusion indexes within voxels of Talairach space, we concluded that the primary epileptogenic focus was in the premotor cortex of the contralateral hemisphere. We then placed the functional data in an anatomic context by adapting a dedicated computerized brain atlas (CBA) to the patient's brain with the aid of magnetic resonance imaging (MRI) slices. By inverse transformation, the patient's data were aligned with the standard geometry of the brain atlas for comparison purposes with data from the literature. The validated activation field projected exactly onto the right precentral sulcus with the anterior border zone including the right frontal eye field.

Atlases as Topic↗
PubMed1990

A partial map of the barley genome incorporating restriction fragment length polymorphism, polymerase chain reaction, isozyme, and morphological marker loci.

Nine low copy number genomic DNA clones, a ribosomal sequence, and seven cDNA clones were found to identify polymorphisms in cultivated barley (Hordeum vulgare L.). An F2 population consisting of 100 plants was produced from a cross between a high-yielding two-rowed feed barley cultivar and a genetic marker stock homozygous for nine recessive and one dominant morphological marker genes. Through the use of these 10 well-distributed marker genes, five previously mapped isozyme loci, and two storage-protein loci, the approximate recombinational location for each of 17 restriction fragment length polymorphism loci was estimated. One clone, pMSU21, identified variation that appeared to be the result of a small insertion-deletion event that differentiated two-rowed and six-rowed genotypes. This difference was characterized, and one allele was sequenced. Oligonucleotide primers that flanked the insertion-deletion event were synthesized, and DNA samples from the F2 population were subjected to polymerase chain reaction sequence amplification. The variation identified by this technique was determined to be allelic to the variation identified using pMSU21 in Southern blot analysis. Maps of previously undescribed informative clones are included.

Base Sequence↗
PubMed2004

Bioie: retargetable information extraction and ontological annotation of biological interactions from the literature.

The need for extracting general biological interactions of arbitrary types from the rapidly growing volume of the biomedical literature is drawing increased attention, while the need for this much diversity also requires both a robust treatment of complex linguistic phenomena and a method to consistently characterize the results. We present a biomedical information extraction system, BioIE, to address both of these needs by utilizing a full-fledged English grammar formalism, or a combinatory categorial grammar, and by annotating the results with the terms of Gene Ontology, which provides a common and controlled vocabulary. BioIE deals with complex linguistic phenomena such as coordination, relative structures, acronyms, appositive structures, and anaphoric expressions. In order to deal with real-world syntactic variations of ontological terms, BioIE utilizes the syntactic dependencies between words in sentences as well, based on the observation that the component words in an ontological term usually appear in a sentence with known patterns of syntactic dependencies.

Abstracting and Indexing↗
PubMed2002

Distribution of eye- and arm-movement-related neuronal activity in the SEF and in the SMA and Pre-SMA of monkeys.

We analyzed neuronal activity in the supplementary eye field (SEF), supplementary motor area (SMA), and presupplementary motor area (pre-SMA) during the performance of three motor tasks: capturing a visual target with a saccade, reaching one arm to a target while gazing at a visual fixation point, or capturing a target with a saccade and arm-reach together. Our data demonstrated that each area was involved in controlling the arm and eye movements in a different manner. Saccade-related neurons were found mainly in the SEF. In contrast, arm-movement-related neurons were found primarily in the SMA and pre-SMA. In addition, we found that the activity of both arm-movement- and saccade-related neurons differed depending on the presence or absence of an accompanying saccade or arm movement. Such context dependency was found in all three areas. We also discovered that activity preceding eye or arm movement alone, and eye and arm movement combined, appeared more often in the pre-SMA and SEF, suggesting their involvement in effector-independent aspects of motor behavior. Subsequent analysis revealed that the laterality of arm representation differed in the three areas: it was predominantly contralateral in the SMA but largely bilateral in the pre-SMA and SEF.

Animals↗
PubMed1997

Reaching movements with similar hand paths but different arm orientations. II. Activity of individual cells in dorsal premotor cortex and parietal area 5.

Reaching movements with similar hand paths but different arm orientations. II. Activity of individual cells in dorsal premotor cortex and parietal area 5. J. Neurophysiol. 78: 2413-2426, 1997. Neuronal activity in primary motor cortex (MI) is altered when monkeys make reaching movements along similar handpaths at shoulder level with two different arm orientations, either in the natural orientation with the elbow positioned below the level of the shoulder and hand or in an abducted orientation with the elbow abducted nearly to shoulder level. The present study examines to what degree two other cortical areas, the dorsal premotor (PMd) and parietal area 5, also show modulation of cell activity related to arm geometry during reaching. The activity of most (89%) of the 207 cells in PMd recorded while monkeys made reaching movements showed a statistically significant change in activity between orientations [analysis of variation (ANOVA), P < 0.01]. A common effect of arm orientation on cell activity was a change in the overall level of discharge either before, during, and/or after movement (67%, ANOVA, task main effect, P < 0.01). Many cells (76%) showed a statistical change in their response to movement direction (ANOVA, task x direction interaction term, P < 0.01), including changes in dynamic range and changes in the preferred direction of cells that were directionally tuned in both arm orientations. Overall, these effects were similar qualitatively but not as strong quantitatively as those observed in MI. A sample of cells was recorded in area 5 of one monkey. Most (95%) of the 79 area 5 cells showed a change in activity when reaching movements were performed using different arm orientations (ANOVA, P < 0.01). As in PMd and MI, many area 5 cells (56, 71%) showed changes in their tonic discharge before, during, and/or after movement, and 70 cells (89%) showed changes in their response to movement direction (ANOVA, task x direction interaction term, P < 0.01). The observed changes in neuronal activity related to posture and movement in MI, PMd and area 5 demonstrate that single-cell activity in these cortical areas is not simply related to the spatial attributes of hand trajectory but is also strongly influenced by attributes of movement related to arm geometry.

Analysis of Variance↗
PubMed2006

Humor comprehension and appreciation: an FMRI study.

Humor is a unique ability in human beings. Suls [A two-stage model for the appreciation of jokes and cartoons. In P. E. Goldstein & J. H. McGhee (Eds.), The psychology of humour. Theoretical perspectives and empirical issues. New York: Academic Press, 1972, pp. 81-100] proposed a two-stage model of humor: detection and resolution of incongruity. Incongruity is generated when a prediction is not confirmed in the final part of a story. To comprehend humor, it is necessary to revisit the story, transforming an incongruous situation into a funny, congruous one. Patient and neuroimaging studies carried out until now lead to different outcomes. In particular, patient studies found that right brain-lesion patients have difficulties in humor comprehension, whereas neuroimaging studies suggested a major involvement of the left hemisphere in both humor detection and comprehension. To prevent activation of the left hemisphere due to language processing, we devised a nonverbal task comprising cartoon pairs. Our findings demonstrate activation of both the left and the right hemispheres when comparing funny versus nonfunny cartoons. In particular, we found activation of the right inferior frontal gyrus (BA 47), the left superior temporal gyrus (BA 38), the left middle temporal gyrus (BA 21), and the left cerebellum. These areas were also activated in a nonverbal task exploring attribution of intention [Brunet, E., Sarfati, Y., Hardy-Bayle, M. C., & Decety, J. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage, 11, 157-166, 2000]. We hypothesize that the resolution of incongruity might occur through a process of intention attribution. We also asked subjects to rate the funniness of each cartoon pair. A parametric analysis showed that the left amygdala was activated in relation to subjective amusement. We hypothesize that the amygdala plays a key role in giving humor an emotional dimension.

Adult↗