scholarly journals Humans and machines in biomedical knowledge curation: hypertrophic cardiomyopathy molecular mechanisms’ representation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mila Glavaški ◽  
Lazar Velicki
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Centrality Measures ◽  
Biomedical Knowledge ◽  
Topological Parameters ◽  
Manual Curation ◽  
Single Reading ◽  
Extraction Performance ◽  
Reading System ◽  
High Level

Abstract Background Biomedical knowledge is dispersed in scientific literature and is growing constantly. Curation is the extraction of knowledge from unstructured data into a computable form and could be done manually or automatically. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, with genotype–phenotype associations still incompletely understood. We compared human- and machine-curated HCM molecular mechanisms’ models and examined the performance of different machine approaches for that task. Results We created six models representing HCM molecular mechanisms using different approaches and made them publicly available, analyzed them as networks, and tried to explain the models’ differences by the analysis of factors that affect the quality of machine-curated models (query constraints and reading systems’ performance). A result of this work is also the Interactive HCM map, the only publicly available knowledge resource dedicated to HCM. Sizes and topological parameters of the networks differed notably, and a low consensus was found in terms of centrality measures between networks. Consensus about the most important nodes was achieved only with respect to one element (calcium). Models with a reduced level of noise were generated and cooperatively working elements were detected. REACH and TRIPS reading systems showed much higher accuracy than Sparser, but at the cost of extraction performance. TRIPS proved to be the best single reading system for text segments about HCM, in terms of the compromise between accuracy and extraction performance. Conclusions Different approaches in curation can produce models of the same disease with diverse characteristics, and they give rise to utterly different conclusions in subsequent analysis. The final purpose of the model should direct the choice of curation techniques. Manual curation represents the gold standard for information extraction in biomedical research and is most suitable when only high-quality elements for models are required. Automated curation provides more substance, but high level of noise is expected. Different curation strategies can reduce the level of human input needed. Biomedical knowledge would benefit overwhelmingly, especially as to its rapid growth, if computers were to be able to assist in analysis on a larger scale.

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

scholarly journals Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 785
Author(s):  
Mila Glavaški ◽  
Lazar Velicki
Keyword(s):  
Cardiovascular Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Open Access ◽  
Molecular Mechanisms ◽  
Scientific Literature ◽  
Automated Extraction ◽  
Clinical Presentations ◽  
Machine Reading ◽  
Pathway Databases

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a prevalence of 1 in 500 people and varying clinical presentations. Although there is much research on HCM, underlying molecular mechanisms are poorly understood, and research on the molecular mechanisms of its specific clinical presentations is scarce. Our aim was to explore the molecular mechanisms shared by HCM and its clinical presentations through the automated extraction of molecular mechanisms. Molecular mechanisms were congregated by a query of the INDRA database, which aggregates knowledge from pathway databases and combines it with molecular mechanisms extracted from abstracts and open-access full articles by multiple machine-reading systems. The molecular mechanisms were extracted from 230,072 articles on HCM and 19 HCM clinical presentations, and their intersections were found. Shared molecular mechanisms of HCM and its clinical presentations were represented as networks; the most important elements in the intersections’ networks were found, centrality scores for each element of each network calculated, networks with reduced level of noise generated, and cooperatively working elements detected in each intersection network. The identified shared molecular mechanisms represent possible mechanisms underlying different HCM clinical presentations. Applied methodology produced results consistent with the information in the scientific literature.

Investigating the resistance levels and mechanisms to penoxsulam and cyhalofop-butyl in barnyardgrass (Echinochloa crus-galli) from Ningxia province, China

Weed Science ◽  
2021 ◽  
pp. 1-25
Author(s):  
Qian Yang ◽  
Xia Yang ◽  
Zichang Zhang ◽  
Jieping Wang ◽  
Weiguo Fu ◽  
...  
Keyword(s):  
Herbicide Resistance ◽  
Molecular Mechanisms ◽  
Acetolactate Synthase ◽  
Rice Fields ◽  
Target Site ◽  
Herbicide Resistant ◽  
Susceptible Populations ◽  
High Level ◽  
Als Inhibitor ◽  
Encoding Genes

Abstract Barnyardgrass (Echinochloa crus-galli) is a noxious grass weed which infests rice fields and causes huge crop yield losses. In this study, we collected twelve E. crus-galli populations from rice fields of Ningxia province in China and investigated the resistance levels to acetolactate synthase (ALS) inhibitor penoxsulam and acetyl-CoA carboxylase (ACCase) inhibitor cyhalofop-butyl. The results showed that eight populations exhibited resistance to penoxsulam and four populations evolved resistance to cyhalofop-butyl. Moreover, all of the four cyhalofop-butyl-resistant populations (NX3, NX4, NX6 and NX7) displayed multiple-herbicide-resistance (MHR) to both penoxsulam and cyhalofop-butyl. The alternative herbicides bispyribac-sodium, metamifop and fenoxaprop-P-ethyl cannot effectively control the MHR plants. To characterize the molecular mechanisms of resistance, we amplified and sequenced the target-site encoding genes in resistant and susceptible populations. Partial sequences of three ALS genes and six ACCase genes were examined. A Trp-574-Leu mutation was detected in EcALS1 and EcALS3 in two high-level (65.84- and 59.30-fold) penoxsulam-resistant populations NX2 and NX10, respectively. In addition, one copy (EcACC4) of ACCase genes encodes a truncated aberrant protein due to a frameshift mutation in E. crus-galli populations. None of amino acid substitutions that are known to confer herbicide resistance were detected in ALS and ACCase genes of MHR populations. Our study reveals the widespread of multiple-herbicide resistant E. crus-galli populations at Ningxia province of China that exhibit resistance to several ALS and ACCase inhibitors. Non-target-site based mechanisms are likely to be involved in E. crus-galli resistance to the herbicides, at least in four MHR populations.

scholarly journals Facilitated Cross-Bridge Interactions with Thin Filaments by Familial Hypertrophic Cardiomyopathy Mutations inα-Tropomyosin

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Fang Wang ◽  
Nicolas M. Brunet ◽  
Justin R. Grubich ◽  
Ewa A. Bienkiewicz ◽  
Thomas M. Asbury ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Helical Structure ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Maximum Speed ◽  
Sliding Speed ◽  
Thin Filaments ◽  
In Vitro Motility ◽  
Cardiac Sarcomeres

Familial hypertrophic cardiomyopathy (FHC) is a disease of cardiac sarcomeres. To identify molecular mechanisms underlying FHC pathology, functional and structural differences in three FHC-related mutations in recombinantα-Tm (V95A, D175N, and E180G) were characterized using both conventional and modified in vitro motility assays and circular dichroism spectroscopy. Mutant Tm's exhibited reducedα-helical structure and increased unordered structure. When thin filaments were fully occupied by regulatory proteins, little or no motion was detected at pCa 9, and maximum speed (pCa 5) was similar for all tropomyosins. Ca2+-responsiveness of filament sliding speed was increased either by increasedpCa50(V95A), reduced cooperativityn(D175N), or both (E180G). When temperature was increased, thin filaments with E180G exhibited dysregulation at temperatures ~10°C lower, and much closer to body temperature, than WT. When HMM density was reduced, thin filaments with D175N required fewer motors to initiate sliding or achieve maximum sliding speed.

scholarly journals Microplate Fluorescence Assay for Measurement of the Ability of Strains of Listeria monocytogenes from Meat and Meat-Processing Plants To Adhere to Abiotic Surfaces

2007 ◽  
Vol 73 (16) ◽  
pp. 5235-5244 ◽  
Author(s):  
Rachel Gamble ◽  
Peter M. Muriana
Keyword(s):  
Listeria Monocytogenes ◽  
Molecular Mechanisms ◽  
Meat Processing ◽  
Abiotic Surfaces ◽  
Food Borne ◽  
Environmental Surfaces ◽  
Processing Plants ◽  
Plate Counts ◽  
Microplate Fluorescence Assay ◽  
High Level

ABSTRACT Listeria monocytogenes is a significant food-borne pathogen that is capable of adhering to and producing biofilms on processing equipment, making it difficult to eliminate from meat-processing environments and allowing potential contamination of ready-to-eat (RTE) products. We devised a fluorescence-based microplate method for screening isolates of L. monocytogenes for the ability to adhere to abiotic surfaces. Strains of L. monocytogenes were incubated for 2 days at 30°C in 96-well microplates, and the plates were washed in a plate washer. The retained cells were incubated for 15 min at 25°C with 5,6-carboxyfluorescein diacetate and washed again, and then the fluorescence was read with a plate reader. Several enzymatic treatments (protease, lipase, and cellulase) were effective in releasing adherent cells from the microplates, and this process was used for quantitation on microbiological media. Strongly adherent strains of L. monocytogenes were identified that had 15,000-fold-higher levels of fluorescence and 100,000-fold-higher plate counts in attachment assays than weakly adherent strains. Strongly adherent strains of L. monocytogenes adhered equally well to four different substrates (glass, plastic, rubber, and stainless steel); showed high-level attachment on microplates at 10, 20, 30, and 40°C; and showed significant differences from weakly adherent strains when examined by scanning electron microscopy. A greater incidence of strong adherence was observed for strains isolated from RTE meats than for those isolated from environmental surfaces. Analysis of surface adherence among Listeria isolates from processing environments may provide a better understanding of the molecular mechanisms involved in attachment and suggest solutions to eliminate them from food-processing environments.

scholarly journals Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice

2019 ◽  
Vol 32 (4) ◽  
pp. 259-272 ◽  
Author(s):  
Moe Tamaura ◽  
Naoko Satoh-Takayama ◽  
Miyuki Tsumura ◽  
Takaharu Sasaki ◽  
Satoshi Goda ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Molecular Mechanisms ◽  
Improve Patient Care ◽  
Chronic Mucocutaneous Candidiasis ◽  
Gain Of Function ◽  
Human Phenotype ◽  
Ifn Γ ◽  
High Level ◽  
Stat1 Protein

Abstract Gain-of-function (GOF) mutations in the gene for signal transducer and activator of transcription 1 (STAT1) account for approximately one-half of patients with chronic mucocutaneous candidiasis (CMC) disease. Patients with GOF-STAT1 mutations display a broad variety of infectious and autoimmune manifestations in addition to CMC, and those with severe infections and/or autoimmunity have a poor prognosis. The establishment of safe and effective treatments based on a precise understanding of the molecular mechanisms of this disorder is required to improve patient care. To tackle this problem, we introduced the human R274Q GOF mutation into mice [GOF-Stat1 knock-in (GOF-Stat1R274Q)]. To investigate the immune responses, we focused on the small intestine (SI), which contains abundant Th17 cells. Stat1R274Q/R274Q mice showed excess phosphorylation of STAT1 in CD4+ T cells upon IFN-γ stimulation, consistent with the human phenotype in patients with the R274Q mutation. We identified two subpopulations of CD4+ T cells, those with ‘normal’ or ‘high’ level of basal STAT1 protein in Stat1R274Q/R274Q mice. Upon IFN-γ stimulation, the ‘normal’ level CD4+ T cells were more efficiently phosphorylated than those from WT mice, whereas the ‘high’ level CD4+ T cells were not, suggesting that the level of STAT1 protein does not directly correlate with the level of pSTAT1 in the SI. Inoculation of Stat1R274Q/R274Q mice with Candida albicans elicited decreased IL-17-producing CD4+RORγt+ cells. Stat1R274Q/R274Q mice also excreted larger amounts of C. albicans DNA in their feces than control mice. Under these conditions, there was up-regulation of T-bet in CD4+ T cells. GOF-Stat1R274Q mice thus should be a valuable model for functional analysis of this disorder.

scholarly journals Chemical–protein interaction extraction via Gaussian probability distribution and external biomedical knowledge

2020 ◽  
Vol 36 (15) ◽  
pp. 4323-4330 ◽  
Author(s):  
Cong Sun ◽  
Zhihao Yang ◽  
Leilei Su ◽  
Lei Wang ◽  
Yin Zhang ◽  
...  
Keyword(s):  
Probability Distribution ◽  
Protein Interactions ◽  
Local Structure ◽  
Relation Extraction ◽  
Biomedical Literature ◽  
Supplementary Information ◽  
Biomedical Knowledge ◽  
Proposed Model ◽  
Gaussian Probability Distribution ◽  
Extraction Performance

Abstract Motivation The biomedical literature contains a wealth of chemical–protein interactions (CPIs). Automatically extracting CPIs described in biomedical literature is essential for drug discovery, precision medicine, as well as basic biomedical research. Most existing methods focus only on the sentence sequence to identify these CPIs. However, the local structure of sentences and external biomedical knowledge also contain valuable information. Effective use of such information may improve the performance of CPI extraction. Results In this article, we propose a novel neural network-based approach to improve CPI extraction. Specifically, the approach first employs BERT to generate high-quality contextual representations of the title sequence, instance sequence and knowledge sequence. Then, the Gaussian probability distribution is introduced to capture the local structure of the instance. Meanwhile, the attention mechanism is applied to fuse the title information and biomedical knowledge, respectively. Finally, the related representations are concatenated and fed into the softmax function to extract CPIs. We evaluate our proposed model on the CHEMPROT corpus. Our proposed model is superior in performance as compared with other state-of-the-art models. The experimental results show that the Gaussian probability distribution and external knowledge are complementary to each other. Integrating them can effectively improve the CPI extraction performance. Furthermore, the Gaussian probability distribution can effectively improve the extraction performance of sentences with overlapping relations in biomedical relation extraction tasks. Availability and implementation Data and code are available at https://github.com/CongSun-dlut/CPI_extraction. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 990
Author(s):  
Jean-Marie Ravel ◽  
L. Cristobal Monraz Gomez ◽  
Nicolas Sompairac ◽  
Laurence Calzone ◽  
Boris Zhivotovsky ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Signaling Network ◽  
Tumor Subtypes ◽  
Navigation Data ◽  
Manual Curation ◽  
Regulated Cell Death ◽  
Powerful Analytical Tool ◽  
Cell Death Signaling ◽  
The Difference

The processes leading to, or avoiding cell death are widely studied, because of their frequent perturbation in various diseases. Cell death occurs in three highly interconnected steps: Initiation, signaling and execution. We used a systems biology approach to gather information about all known modes of regulated cell death (RCD). Based on the experimental data retrieved from literature by manual curation, we graphically depicted the biological processes involved in RCD in the form of a seamless comprehensive signaling network map. The molecular mechanisms of each RCD mode are represented in detail. The RCD network map is divided into 26 functional modules that can be visualized contextually in the whole seamless network, as well as in individual diagrams. The resource is freely available and accessible via several web platforms for map navigation, data integration, and analysis. The RCD network map was employed for interpreting the functional differences in cell death regulation between Alzheimer’s disease and non-small cell lung cancer based on gene expression data that allowed emphasizing the molecular mechanisms underlying the inverse comorbidity between the two pathologies. In addition, the map was used for the analysis of genomic and transcriptomic data from ovarian cancer patients that provided RCD map-based signatures of four distinct tumor subtypes and highlighted the difference in regulations of cell death molecular mechanisms.

scholarly journals Mimics of Hypertrophic Cardiomyopathy – Diagnostic Clues to Aid Early Identification of Phenocopies

2013 ◽  
Vol 2 (1) ◽  
pp. 36 ◽  
Author(s):  
Rajiv Sankaranarayanan ◽  
Eleanor J Fleming ◽  
Clifford J Garratt ◽  
◽  
◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hypertrophic Cardiomyopathy ◽  
Early Identification ◽  
Inborn Errors Of Metabolism ◽  
Early Stage ◽  
Inborn Errors ◽  
Sarcomeric Mutations ◽  
Widespread Availability ◽  
High Level ◽  
Storage Disorders

Hypertrophic cardiomyopathy (HCM) is the most common genetic cause of cardiomyopathy worldwide. Significant advances and widespread availability of genetic testing have improved detection of the sarcomeric mutations that cause HCM, but have also highlighted the significance of inborn errors of metabolism (IEM) or metabolic storage disorders that can mimic HCM (‘HCM phenocopies’). These conditions cannot always be reliably differentiated on the basis of imaging alone. Whilst HCM phenocopies are relatively rare, it is crucial to distinguish these conditions at an early stage as their natural history, management and prognosis vary significantly from that of HCM with sarcomeric mutations. This review illustrates the salient features of HCM phenocopies and stresses the need for a high level of suspicion for these conditions in the assessment of cardiac hypertrophy.

scholarly journals Chromosomally and Extrachromosomally Mediated High-Level Gentamicin Resistance in Streptococcus agalactiae

2016 ◽  
Vol 60 (3) ◽  
pp. 1702-1707 ◽  
Author(s):  
Parham Sendi ◽  
Martina Furitsch ◽  
Stefanie Mauerer ◽  
Carlos Florindo ◽  
Barbara C. Kahl ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Streptococcus Agalactiae ◽  
Molecular Mechanisms ◽  
The Other ◽  
Content Type ◽  
Gentamicin Resistance ◽  
Group B ◽  
High Level ◽  
Plasmid Purification

Streptococcus agalactiae(group BStreptococcus[GBS]) is a leading cause of sepsis in neonates. The rate of invasive GBS disease in nonpregnant adults also continues to climb. Aminoglycosides alone have little or no effect on GBS, but synergistic killing with penicillin has been shownin vitro. High-level gentamicin resistance (HLGR) in GBS isolates, however, leads to the loss of a synergistic effect. We therefore performed a multicenter study to determine the frequency of HLGR GBS isolates and to elucidate the molecular mechanisms leading to gentamicin resistance. From eight centers in four countries, 1,128 invasive and colonizing GBS isolates were pooled and investigated for the presence of HLGR. We identified two strains that displayed HLGR (BSU1203 and BSU452), both of which carried theaacA-aphDgene, typically conferring HLGR. However, only one strain (BSU1203) also carried the previously described chromosomal gentamicin resistance transposon designated Tn3706. For the other strain (BSU452), plasmid purification and subsequent DNA sequencing resulted in the detection of plasmid pIP501 carrying a remnant of a Tn3family transposon. Its ability to confer HLGR was proven by transfer into anEnterococcus faecalisisolate. Conversely, loss of HLGR was documented after curing both GBS BSU452 and the transformedE. faecalisstrain from the plasmid. This is the first report showing plasmid-mediated HLGR in GBS. Thus, in our clinical GBS isolates, HLGR is mediated both chromosomally and extrachromosomally.

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