CSI-OMIM - Clinical Synopsis Search in OMIM

Background  

The OMIM database is a tool used daily by geneticists. Syndrome pages include a Clinical Synopsis section containing a list of known phenotypes comprising a clinical syndrome. The phenotypes are in free text and different phrases are often used to describe the same phenotype, the differences originating in spelling variations or typing errors, varying sentence structures and terminological variants.     

Automated extraction of information in molecular biology

We review data mining techniques in molecular biology, specifically those that extract information from the scientific literature itself. As more of the biological literature is published electronically, there is an opportunity, and even a need, to automatically summarize the literature in a customized way, for example by associating keywords to a topic. These keywords can be extracted from relevant publications. The process of keyword extraction can be automated and optimized to keep literature pointers automatically up-to-date or to filter relevant information from the literature. To illustrate these points, OMIM (Online Mendelian Inheritance in Man), a database of human inherited diseases, was linked to the literature and keywords were derived that covered distinct aspects such as genetic information on the one hand and disease-specific protein and phenotypic information on the other. They were used to extract information that is helpful for keeping entries about disease up-to-date.     

Automatic extraction of mutations from Medline and cross-validation with OMIM

Mutations help us to understand the molecular origins of diseases. Researchers, therefore, both publish and seek disease-relevant mutations in public databases and in scientific literature, e.g. Medline. The retrieval tends to be time-consuming and incomplete. Automated screening of the literature is more efficient. We developed extraction methods (called MEMA) that scan Medline abstracts for mutations. MEMA identified 24,351 singleton mutations in conjunction with a HUGO gene name out of 16,728 abstracts. From a sample of 100 abstracts we estimated the recall for the identification of mutation-gene pairs to 35% at a precision of 93%. Recall for the mutation detection alone was >67% with a precision rate of >96%. This shows that our system produces reliable data. The subset consisting of protein sequence mutations (PSMs) from MEMA was compared to the entries in OMIM (20,503 entries versus 6699, respectively). We found 1826 PSM-gene pairs to be in common to both datasets (cross-validated). This is 27% of all PSM-gene pairs in OMIM and 91% of those pairs from OMIM which co-occur in at least one Medline abstract. We conclude that Medline covers a large portion of the mutations known to OMIM. Another large portion could be artificially produced mutations from mutagenesis experiments. Access to the database of extracted mutation-gene pairs is available through the web pages of the EBI (refer to http://www.ebi. ac.uk/rebholz/index.html).     

Gut–organ axis: a microbial outreach and networking

Human gut microbiota (GM) includes a complex and dynamic population of microorganisms that are crucial for well-being and survival of the organism. It has been reported as diverse and relatively stable with shared core microbiota, including Bacteroidetes and Firmicutes as the major dominants. They are the key regulators of body homeostasis, involving both intestinal and extra-intestinal effects by influencing many physiological functions such as metabolism, maintenance of barrier homeostasis, inflammation and hematopoiesis. Any alteration in GM community structures not only trigger gut disorders but also influence other organs and cause associated diseases. In recent past, the GM has been defined as a ‘vital organ’ with its involvement with other organs; thus, establishing a link or a bi- or multidirectional communication axis between the organs via neural, endocrine, immune, humoral and metabolic pathways. Alterations in GM have been linked to several diseases known to humans; although the exact interaction mechanism between the gut and the organs is yet to be defined. In this review, the bidirectional relationship between the gut and the vital human organs was envisaged and discussed under several headings. Furthermore, several disease symptoms were also revisited to redefine the communication network between the gut microbes and the associated organs.     

Text processing through Web services: calling Whatizit

MOTIVATION: Text-mining (TM) solutions are developing into efficient services to researchers in the biomedical research community. Such solutions have to scale with the growing number and size of resources (e.g. available controlled vocabularies), with the amount of literature to be processed (e.g. about 17 million documents in PubMed) and with the demands of the user community (e.g. different methods for fact extraction). These demands motivated the development of a server-based solution for literature analysis. Whatizit is a suite of modules that analyse text for contained information, e.g. any scientific publication or Medline abstracts. Special modules identify terms and then link them to the corresponding entries in bioinformatics databases such as UniProtKb/Swiss-Prot data entries and gene ontology concepts. Other modules identify a set of selected annotation types like the set produced by the EBIMed analysis pipeline for proteins. In the case of Medline abstracts, Whatizit offers access to EBI's in-house installation via PMID or term query. For large quantities of the user's own text, the server can be operated in a streaming mode (http://www.ebi.ac.uk/webservices/whatizit).     

CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM) to identify genetically-associated cancers and candidate genes

Background  

Online Mendelian Inheritance in Man (OMIM) is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results.     

The emergence of somatotopic maps of the body in S1 in rats: the correspondence between functional and anatomical organization

Most of what we know about cortical map development and plasticity comes from studies in mice and rats, and for the somatosensory cortex, almost exclusively from the whisker-dominated posteromedial barrel fields. Whiskers are the main effector organs of mice and rats, and their representation in cortex and subcortical pathways is a highly derived feature of murine rodents. This specialized anatomical organization may therefore not be representative of somatosensory cortex in general, especially for species that utilize other body parts as their main effector organs, like the hands of primates. For these reasons, we examined the emergence of whole body maps in developing rats using electrophysiological recording techniques. In P5, P10, P15, P20 and adult rats, multiple recordings were made in the medial portion of S1 in each animal. Subsequently, these functional maps were related to anatomical parcellations of S1 based on a variety of histological stains. We found that at early postnatal ages (P5) medial S1 was composed almost exclusively of the representation of the vibrissae. At P10, other body part representations including the hindlimb and forelimb were present, although these were not topographically organized. By P15, a clear topographic organization began to emerge coincident with a reduction in receptive field size. By P20, body maps were adult-like. This study is the first to describe how topography of the body develops in S1 in any mammal. It indicates that anatomical parcellations and functional maps are initially incongruent but become tightly coupled by P15. Finally, because anatomical and functional specificity of developing barrel cortex appears much earlier in postnatal life than the rest of the body, the entire primary somatosensory cortex should be considered when studying general topographic map formation in development.     

Iron in blood cells: Function,relation to disease,and potential for magnetic separation

Iron in blood cells has several physiological functions like transporting oxygen to cells and maintaining iron homeostasis. Iron is primarily contained in red blood cells (RBCs), but monocytes also store iron as these cells are responsible for the recycling of senescent RBCs. Iron also serves an important role related to the function of different leukocytes. In inflammation, iron homeostasis is dependent on cytokines derived from T cells and macrophages. Fluctuations of iron content in the body lead to different diseases. Iron deficiency, which is also known as anemia, hampers different physiological processes in the human body. On the other hand, genetic or acquired hemochromatosis ultimately results in iron overload and leads to the failure of different vital organs. Different diagnoses and treatments are developed for these kinds of disorders, but the majority are costly and suffer from side effects. To address this issue, magnetophoresis could be an attractive technology for the diagnosis (and in some cases treatment) of these pathologies due to the paramagnetic character of the cells containing iron. In this review, we discuss the main functions of iron in blood cells and iron-related diseases in humans and highlight the potential of magnetophoresis for diagnosing and treating some of these disorders.     

KinMutBase, a database of human disease-causing protein kinase mutations

KinMutBase (http://www.uta.fi/imt/bioinfo/KinMutBase/) is a registry of mutations in human protein kinases related to disorders. Kinases are essential cellular signaling molecules, in which mutations can lead to diseases, including immunodeficiencies, cancers and endocrine disorders. The first release of KinMutBase contained information for protein tyrosine kinases. The current release includes also serine/threonine protein kinases, as well as an update of the tyrosine kinases. There are 251 entries altogether, representing 337 families and 621 patients. Mutations appear both in conserved hallmark residues of the kinases as well as in non-homologous sites. The KinMutBase WWW pages provide plenty of information, namely mutation statistics and display, clickable sequences with mutations and changes to restriction enzyme patterns.     

Effectively processing medical term queries on the UMLS Metathesaurus by layered dynamic programming

Background

Mapping medical terms to standardized UMLS concepts is a basic step for leveraging biomedical texts in data management and analysis. However, available methods and tools have major limitations in handling queries over the UMLS Metathesaurus that contain inaccurate query terms, which frequently appear in real world applications.

Methods

To provide a practical solution for this task, we propose a layered dynamic programming mapping (LDPMap) approach, which can efficiently handle these queries. LDPMap uses indexing and two layers of dynamic programming techniques to efficiently map a biomedical term to a UMLS concept.

Results

Our empirical study shows that LDPMap achieves much faster query speeds than LCS. In comparison to the UMLS Metathesaurus Browser and MetaMap, LDPMap is much more effective in querying the UMLS Metathesaurus for inaccurately spelled medical terms, long medical terms, and medical terms with special characters.

Conclusions

These results demonstrate that LDPMap is an efficient and effective method for mapping medical terms to the UMLS Metathesaurus.

     

Tetrazolium salts: a consumer's guide

Synopsis The purities of seven tetrazolium salts, obtained from various commercial sources, have been assessed by thin layer chromatography, relative extinction coefficients, and melting points. MTT and INT were largely homogeneous on thin layer chromatography, although significant variations occurred in the melting point behaviour. All the samples of TT examined were contaminated to a small extent with non-tetrazolium u.v.-absorbing material. TNBT and NBT were contaminated with small amounts of mono-tetrazolium salts, although one sample of each was heavily contaminated with another di-tetrazolium compound. Four samples of TNBT contained high melting point contaminants. BT was also contaminated with mono-tetrazolium salts, and some samples also contained di-tetrazolium salt contaminants. NT was the most heavily contaminated of all, most samples containing no less than five separate tetrazolium compounds. Prices varied widely, and in general were not related to purity. Some catalogue entries were very easy to find; others were more difficult. Few specifications were given; of these, most were arbitrary (for example, pure, grade I, and ... probably the finest INT offered anywhere).     

Developmental causes of allometry: new models and implications for phenotypic plasticity and evolution

Shapes change during development because tissues, organs, and various anatomical features differ in onset, rate, and duration of growth. Allometry is the study of the consequences of differences in the growth of body parts on morphology, although the field of allometry has been surprisingly little concerned with understanding the causes of differential growth. The power-law equation y?=?ax(b), commonly used to describe allometries, is fundamentally an empirical equation whose biological foundation has been little studied. Huxley showed that the power-law equation can be derived if one assumes that body parts grow with exponential kinetics, for exactly the same amount of time. In life, however, the growth of body parts is almost always sigmoidal, and few, if any, grow for exactly the same amount of time during ontogeny. Here, we explore the shapes of allometries that result from real growth patterns and analyze them with new allometric equations derived from sigmoidal growth kinetics. We use an extensive ontogenetic dataset of the growth of internal organs in the rat from birth to adulthood, and show that they grow with Gompertz sigmoid kinetics. Gompertz growth parameters of body and internal organs accurately predict the shapes of their allometries, and that nonlinear regression on allometric data can accurately estimate the underlying kinetics of growth. We also use these data to discuss the developmental relationship between static and ontogenetic allometries. We show that small changes in growth kinetics can produce large and apparently qualitatively different allometries. Large evolutionary changes in allometry can be produced by small and simple changes in growth kinetics, and we show how understanding the development of traits can greatly simplify the interpretation of how they evolved.     

Histone Sequence Database: sequences, structures, post-translational modifications and genetic loci.

The Histone Sequence Database is an annotated and searchable collection of all available histone and histone fold sequences and structures. Particular emphasis has been placed on documenting conflicts between similar sequence entries from a number of source databases, conflicts that are not necessarily documented in the source databases themselves. New additions to the database include compilations of post-translational modifications for each of the core and linker histones, as well as genomic information in the form of map loci for the human histone gene complement, with the genetic loci linked to Online Mendelian Inheritance in Man (OMIM). The database is freely accessible through the World Wide Web at either http://genome.nhgri.nih.gov/histones/ or http://www.ncbi.nlm.nih. gov/Baxevani/HISTONES     

The hypothalamus for whole-body physiology: from metabolism to aging

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.     

Clinical whole exome sequencing revealed de novo heterozygous stop-gain and missense variants in the STXBP1 gene associated with epilepsy in Saudi families

Intellectual disability and developmental encephalopathies are mostly linked with infant epilepsy. Epileptic encephalopathy is a term that is used to define association between developmental delay and epilepsy. Mutations in the STXBP1 (Syntaxin-binding protein 1) gene have been previously reported in association with multiple severe early epileptic encephalopathies along with many neurodevelopmental disorders. Among the disorders produced due to any mutations in the STXBP1 gene is developmental and epileptic encephalopathy 4 (OMIM: 612164), is an autosomal dominant neurologic disorder categorized by the onset of tonic seizures in early infancy (usually in the first months of life). In this article, we report two Saudi families one with de novo heterozygous stop-gain mutation c.364C > T and a novel missense c. 305C > A p.Ala102Glu in exon 5 of the STXBP1 gene (OMIM: 602926) lead to development of epileptic encephalopathy 4. The variants identified in the current study broadened the genetic spectrum of STXBP1 gene related with diseases, which will help to add in the literature and benefit to the studies addressing this disease in the future.     

Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective

There are over 40 identified human disorders that involve certain proteins folding incorrectly, accumulating in the body causing damage to cells and organs and causing disease. Type 2 Diabetes Mellitus (T2DM) is one of these protein misfolding disorders (PMDs) and involves human islet amyloid polypeptide (hIAPP) misfolding and accumulating in parts of the body, primarily in the pancreas, causing damage to islet cells and affecting glucose regulation. In this review, we have summarised our current understanding of what causes hIAPP to misfold, what conformations are found in different parts of the body with a particular focus on what is known about the structure of hIAPP and how this links to T2DM. Understanding the molecular basis behind these misfolding events is essential for understanding the role of hIAPP to develop better therapeutics since type 2 diabetes currently affects over 4.9 million people in the United Kingdom alone and is predicted to increase as our population ages.     

基于网络药理学、分子对接和实验验证探讨朱茯苓用于失眠的作用机制

为探讨朱茯苓治疗失眠的可能作用机制,通过TCMSP、BAT-MAN、TCMID和STITCH数据库以及文献挖掘筛选朱茯苓的活性成分及潜在靶点,利用TTD、OMIM、GeneCards和CTD数据库获取失眠类疾病的相关靶点,采用Cyto-scape软件和String数据库构建活性成分-靶点网络和靶点蛋白相互作用网络,通过...     

Anatomical variants of the lymphatic vessels connecting the inguinal lymph nodes]

The study of anatomical variants of lymphatic vessels connecting inguinal lymph nodes was carried out on 56 corpses of adult persons of both sex whose deaths were not connected with lesions in the lymphatic system of the pelvis and lower extremities. The inguinal lymph nodes and their afferent and efferent lymphatic vessels were detected by the method of intradermal injection and by the method of direct injection into the lymphatic vessels. It was stated that groups of the inguinal lymph nodes, as well as the nodes in every group determined, can serve as nodes of different stages for afferent lymphatic vessels running from different parts of the body and organs.     

Molecular basis of X-linked non-specific mental retardation

Mental retardation (MR) is a common disorder, affecting 1-3% of the total population. This condition results from failure to develop cognitive abilities and intelligence level appropriate for the age group. Mental retardation is basically a clinically as well as etiologically heterogeneous type of condition and both genetic and non-genetic factors have been found to be involved. There are more than 1000 entries in Online Mendelian Inheritance in Man (OMIM) database under the name of mental retardation. In recent years 15 genes for X linked non-specific mental retardation have been identified which provide important clues regarding molecular and cellular processes involved in signal transduction cascade in central nervous system. Recent advancements in identification and characterization of X-linked non-specific mental retardation genes have been discussed in this review. Understanding of the molecular pathways of disease causing genes would be helpful in developing effective therapeutic approaches for mental retardation.     

脑网络：从脑结构到脑功能

人脑是自然界中最复杂的系统之一,不同的功能区域相互作用、互相协调,共同构成一个网络来发挥其功能。人脑是一个复杂的网络,具有高效的“小世界”拓扑属性。本文从脑结构到脑功能方面介绍了从不同模态影像学数据构造脑网络的主要进展,并探讨不同的脑疾病患者脑网络拓扑结构是否发生了异常,以及这些异常特征能否用来进行疾病分类,最后对本领域未来的研究做了简单的展望。