Classification of non-coding variants with high pathogenic impact

2021 ◽  
Author(s):  
Jeffrey Calhoun
Keyword(s):  
Coding Variants ◽  
High Pathogenic

scholarly journals Prediction and interpretation of deleterious coding variants in terms of protein structural stability

2017 ◽  
Author(s):  
F. Ancien ◽  
F. Pucci ◽  
M. Godfroid ◽  
M. Rooman
Keyword(s):  
Positive Predictive Value ◽  
Predictive Value ◽  
Solvent Accessibility ◽  
Synonymous Mutations ◽  
Knowledge Based ◽  
Stability Change ◽  
High Positive Predictive Value ◽  
Stability Issues ◽  
Coding Variants

ABSTRACTThe classification of human genetic variants into deleterious and neutral is a challenging issue, whose complexity is rooted in the large variety of biophysical mechanisms that can be responsible for disease conditions. For non-synonymous mutations in structured proteins, one of these is the protein stability change, which can lead to functionality loss. We developed a stability-driven knowledge-based classifier that uses protein structure, artificial neural networks and solvent accessibility-dependent combinations of statistical potentials to predict whether destabilizing or stabilizing mutations are disease-causing. Our predictor yields a balanced accuracy of 71% in cross validation. As expected, it has a very high positive predictive value of 89%: it predicts with high accuracy the subset of mutations that are deleterious because of stability issues, but is by construction unable of classifying variants that are deleterious for other reasons. Its combination with an evolutionary-based predictor increases the balanced accuracy up to 75%, and allowed predicting more than 1/4 of the deleterious variants with 95% positive predictive value. Our method, called SNPMuSiC, can be used with both experimental and structural models and compares favorably with other prediction tools on several independent test sets. It constitutes a step towards interpreting variant effects at the molecular scale.

scholarly journals Classification of non-coding variants with high pathogenic impact

2021 ◽  
Author(s):  
Lambert Moyon ◽  
Camille Berthelot ◽  
Alexandra Louis ◽  
Nga Thi Thuy Nguyen ◽  
Hugues Roest Crollius
Keyword(s):  
Personalised Medicine ◽  
Clinical Settings ◽  
Functional Interpretation ◽  
Protein Coding ◽  
Wide Range ◽  
Machine Learning Approach ◽  
Functional Consequences ◽  
Control Optimisation ◽  
Coding Variants

Whole genome sequencing is increasingly used to diagnose medical conditions of genetic origin. While both coding and non-coding DNA variants contribute to a wide range of diseases, most patients who receive a WGS-based diagnosis today harbour a protein-coding mutation. Functional interpretation and prioritization of non-coding variants represents a persistent challenge, and disease-causing non-coding variants remain largely unidentified. Depending on the disease, WGS fails to identify a candidate variant in 20-80% of patients, severely limiting the usefulness of sequencing for personalised medicine. Here we present FINSURF, a machine-learning approach to predict the functional impact of non-coding variants in regulatory regions. FINSURF outperforms state-of-the-art methods, owing to control optimisation during training. In addition to ranking candidate variants, FINSURF also delivers diagnostic information on functional consequences of mutations. We applied FINSURF to a diverse set of 30 diseases with described causative non-coding mutations, and correctly identified the disease-causative non-coding variant within the ten top hits in 22 cases. FINSURF is implemented as an online server to as well as custom browser tracks, and provides a quick and efficient solution to prioritize candidate non-coding variants in realistic clinical settings.

Note on the spectral classification of carbon stars in the photographic infrared region

1966 ◽  
Vol 24 ◽  
pp. 21-23
Author(s):  
Y. Fujita
Keyword(s):  
Infrared Region ◽  
Spectral Classification ◽  
Carbon Stars

We have investigated the spectrograms (dispersion: 8Å/mm) in the photographic infrared region fromλ7500 toλ9000 of some carbon stars obtained by the coudé spectrograph of the 74-inch reflector attached to the Okayama Astrophysical Observatory. The names of the stars investigated are listed in Table 1.

Diagnostic Value of Electron Microscopy in Soft Tissue Tumors

1970 ◽  
Vol 28 ◽  
pp. 220-221
Author(s):  
Gerald Fine ◽  
Azorides R. Morales
Keyword(s):  
Cardiac Myxoma ◽  
Osteogenic Sarcoma ◽  
Diagnostic Value ◽  
Soft Tissue Tumors ◽  
Amelanotic Melanoma ◽  
Growth Patterns ◽  
Light Microscopic Level ◽  
Mesenchymal Tumors ◽  
Good Agreement

For years the separation of carcinoma and sarcoma and the subclassification of sarcomas has been based on the appearance of the tumor cells and their microscopic growth pattern and information derived from certain histochemical and special stains. Although this method of study has produced good agreement among pathologists in the separation of carcinoma from sarcoma, it has given less uniform results in the subclassification of sarcomas. There remain examples of neoplasms of different histogenesis, the classification of which is questionable because of similar cytologic and growth patterns at the light microscopic level; i.e. amelanotic melanoma versus carcinoma and occasionally sarcoma, sarcomas with an epithelial pattern of growth simulating carcinoma, histologically similar mesenchymal tumors of different histogenesis (histiocytoma versus rhabdomyosarcoma, lytic osteogenic sarcoma versus rhabdomyosarcoma), and myxomatous mesenchymal tumors of diverse histogenesis (myxoid rhabdo and liposarcomas, cardiac myxoma, myxoid neurofibroma, etc.)

Ultrastructure of mesotheliomas

1984 ◽  
Vol 42 ◽  
pp. 98-101
Author(s):  
Irving Dardick
Keyword(s):  
Electron Microscopy ◽  
Latent Period ◽  
Spindle Cell ◽  
Spindle Cell Sarcoma ◽  
Metastatic Adenocarcinoma ◽  
Cell Sarcoma ◽  
Cytological Features ◽  
Industrial Use ◽  
Degree Of Differentiation

With the extensive industrial use of asbestos in this century and the long latent period (20-50 years) between exposure and tumor presentation, the incidence of malignant mesothelioma is now increasing. Thus, surgical pathologists are more frequently faced with the dilemma of differentiating mesothelioma from metastatic adenocarcinoma and spindle-cell sarcoma involving serosal surfaces. Electron microscopy is amodality useful in clarifying this problem.In utilizing ultrastructural features in the diagnosis of mesothelioma, it is essential to appreciate that the classification of this tumor reflects a variety of morphologic forms of differing biologic behavior (Table 1). Furthermore, with the variable histology and degree of differentiation in mesotheliomas it might be expected that the ultrastructure of such tumors also reflects a range of cytological features. Such is the case.

Interpreting HVEM of muscle-cell impulse networks

1992 ◽  
Vol 50 (1) ◽  
pp. 126-127
Author(s):  
Paul DeCosta ◽  
Kyugon Cho ◽  
Stephen Shemlon ◽  
Heesung Jun ◽  
Stanley M. Dunn
Keyword(s):  
Structural Analysis ◽  
Muscle Cell ◽  
Electron Micrographs ◽  
Relative Size ◽  
Automatic Classification ◽  
Nerve Fibers ◽  
Analysis Algorithm ◽  
Structural Networks

Introduction: The analysis and interpretation of electron micrographs of cells and tissues, often requires the accurate extraction of structural networks, which either provide immediate 2D or 3D information, or from which the desired information can be inferred. The images of these structures contain lines and/or curves whose orientation, lengths, and intersections characterize the overall network.Some examples exist of studies that have been done in the analysis of networks of natural structures. In, Sebok and Roemer determine the complexity of nerve structures in an EM formed slide. Here the number of nodes that exist in the image describes how dense nerve fibers are in a particular region of the skin. Hildith proposes a network structural analysis algorithm for the automatic classification of chromosome spreads (type, relative size and orientation).

Dual stain kit for the microscopic gram classification of ocular infection bacteria

1993 ◽  
Vol 51 ◽  
pp. 248-249
Author(s):  
Jacob S. Hanker ◽  
Dale N. Holdren ◽  
Kenneth L. Cohen ◽  
Beverly L. Giammara
Keyword(s):  
Contact Lenses ◽  
Ocular Infection ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Staining ◽  
Ocular Infections ◽  
Different Types ◽  
Culture Positive ◽  
Increased Susceptibility

Keratitis and conjunctivitis (infections of the cornea or conjunctiva) are ocular infections caused by various bacteria, fungi, viruses or parasites; bacteria, however, are usually prominent. Systemic conditions such as alcoholism, diabetes, debilitating disease, AIDS and immunosuppressive therapy can lead to increased susceptibility but trauma and contact lens use are very important factors. Gram-negative bacteria are most frequently cultured in these situations and Pseudomonas aeruginosa is most usually isolated from culture-positive ulcers of patients using contact lenses. Smears for staining can be obtained with a special swab or spatula and Gram staining frequently guides choice of a therapeutic rinse prior to the report of the culture results upon which specific antibiotic therapy is based. In some cases staining of the direct smear may be diagnostic in situations where the culture will not grow. In these cases different types of stains occasionally assist in guiding therapy.

Ultrastructural Classification of Pituary Adenomas

1990 ◽  
Vol 48 (3) ◽  
pp. 258-258
Author(s):  
S. Arumugam ◽  
Sarasa Bharati Arumugam
Keyword(s):  
Cytoplasmic Organelle ◽  
Null Cell ◽  
Cell Adenoma ◽  
Mixed Cell ◽  
Light Microscope Level ◽  
Null Cell Adenoma ◽  
Growth Hormone Cell ◽  
Ultrastructural Characteristics ◽  
Organelle Morphology

Adenoaas of the pituitary are no longer classified based on their tinctorial affinity to dyes. With the advent of the newer methods of sophisticated technology, it is now possible to classify. These depending upon the type of hormone secreted based either on histochemical techniques or on ultrastructural characteristics. The latter provides an insight into the cytoplasmic organelle morphology which offers a delightful feast to the eye as well.This paper presents the ultrastructural characters of the pituitary adenoma as seen in Madras. 171 adenomas (124 males and 47 females) were seen during 1972-1989, classified at the light microscope level as 159 chromophobe, 2 basophilic, 4 eosinophilic and 6 mixed adenomas.Ultrastructural examination showed that the sparsely granular prolactin cell adenoma is the commonest adenoma to be encountered closely followed by the growth hormone cell adenoma, null cell adenoma, the mixed cell adenoma and others.

Consistency in Latency Measurements and Interpretation of ABR Tracings

1997 ◽  
Vol 6 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Wayne O. Olsen ◽  
Terri L. Pratt ◽  
Christopher D. Bauch
Keyword(s):  
The Other

Multichannel ABR recordings for 30 otoneurologic patients were reviewed independently by three audiologists to assess interjudge consistency in determining absolute latencies and overall interpretation of ABR results. Four months later, the tracings were reviewed a second time to evaluate intrajudge consistency in interpretation of ABR waveforms. Interjudge agreement in marking latencies for waves I, III, and V within 0.2 ms was on the order of 90% or better. Intrajudge consistency was slightly higher. Only rarely did inter- or intrajudge differences in latency measurements exceed 0.3 ms. Agreement in overall interpretation of ABR results as "normal" or "abnormal" was unanimous for 90% of the patients. Across pairs of judges, the agreement for "normal" and "abnormal" classification of the ABR tracings was 97%. Intrajudge consistency for "normal" and "abnormal" categorization of the ABR results was 100% for one judge, 97% for the other two judges.

Classification of Infant Vocalizations by Untrained Listeners

2019 ◽  
Vol 62 (9) ◽  
pp. 3265-3275
Author(s):  
Heather L. Ramsdell-Hudock ◽  
Anne S. Warlaumont ◽  
Lindsey E. Foss ◽  
Candice Perry
Keyword(s):  
Formal Education ◽  
Additional Insight ◽  
Listener Responses ◽  
Infant Vocalization ◽  
Early Infant ◽  
Infant Vocalizations ◽  
Audio Recordings ◽  
Speech And Language Development ◽  
Insight Into

Purpose To better enable communication among researchers, clinicians, and caregivers, we aimed to assess how untrained listeners classify early infant vocalization types in comparison to terms currently used by researchers and clinicians. Method Listeners were caregivers with no prior formal education in speech and language development. A 1st group of listeners reported on clinician/researcher-classified vowel, squeal, growl, raspberry, whisper, laugh, and cry vocalizations obtained from archived video/audio recordings of 10 infants from 4 through 12 months of age. A list of commonly used terms was generated based on listener responses and the standard research terminology. A 2nd group of listeners was presented with the same vocalizations and asked to select terms from the list that they thought best described the sounds. Results Classifications of the vocalizations by listeners largely overlapped with published categorical descriptors and yielded additional insight into alternate terms commonly used. The biggest discrepancies were found for the vowel category. Conclusion Prior research has shown that caregivers are accurate in identifying canonical babbling, a major prelinguistic vocalization milestone occurring at about 6–7 months of age. This indicates that caregivers are also well attuned to even earlier emerging vocalization types. This supports the value of continuing basic and clinical research on the vocal types infants produce in the 1st months of life and on their potential diagnostic utility, and may also help improve communication between speech-language pathologists and families.

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