PEDIA: prioritization of exome data by image analysis.

PURPOSE: Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. METHODS: Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. RESULTS: The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20-89% and the top 10 accuracy rate by more than 5-99% for the disease-causing gene. CONCLUSION: Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Multi modal multi-semantic image retrieval

PhDThe rapid growth in the volume of visual information, e.g. image, and video can overwhelm users’ ability to find and access the specific visual information of interest to them. In recent years, ontology knowledge-based (KB) image information retrieval techniques have been adopted into in order to attempt to extract knowledge from these images, enhancing the retrieval performance. A KB framework is presented to promote semi-automatic annotation and semantic image retrieval using multimodal cues (visual features and text captions). In addition, a hierarchical structure for the KB allows metadata to be shared that supports multi-semantics (polysemy) for concepts. The framework builds up an effective knowledge base pertaining to a domain specific image collection, e.g. sports, and is able to disambiguate and assign high level semantics to ‘unannotated’ images. Local feature analysis of visual content, namely using Scale Invariant Feature Transform (SIFT) descriptors, have been deployed in the ‘Bag of Visual Words’ model (BVW) as an effective method to represent visual content information and to enhance its classification and retrieval. Local features are more useful than global features, e.g. colour, shape or texture, as they are invariant to image scale, orientation and camera angle. An innovative approach is proposed for the representation, annotation and retrieval of visual content using a hybrid technique based upon the use of an unstructured visual word and upon a (structured) hierarchical ontology KB model. The structural model facilitates the disambiguation of unstructured visual words and a more effective classification of visual content, compared to a vector space model, through exploiting local conceptual structures and their relationships. The key contributions of this framework in using local features for image representation include: first, a method to generate visual words using the semantic local adaptive clustering (SLAC) algorithm which takes term weight and spatial locations of keypoints into account. Consequently, the semantic information is preserved. Second a technique is used to detect the domain specific ‘non-informative visual words’ which are ineffective at representing the content of visual data and degrade its categorisation ability. Third, a method to combine an ontology model with xi a visual word model to resolve synonym (visual heterogeneity) and polysemy problems, is proposed. The experimental results show that this approach can discover semantically meaningful visual content descriptions and recognise specific events, e.g., sports events, depicted in images efficiently. Since discovering the semantics of an image is an extremely challenging problem, one promising approach to enhance visual content interpretation is to use any associated textual information that accompanies an image, as a cue to predict the meaning of an image, by transforming this textual information into a structured annotation for an image e.g. using XML, RDF, OWL or MPEG-7. Although, text and image are distinct types of information representation and modality, there are some strong, invariant, implicit, connections between images and any accompanying text information. Semantic analysis of image captions can be used by image retrieval systems to retrieve selected images more precisely. To do this, a Natural Language Processing (NLP) is exploited firstly in order to extract concepts from image captions. Next, an ontology-based knowledge model is deployed in order to resolve natural language ambiguities. To deal with the accompanying text information, two methods to extract knowledge from textual information have been proposed. First, metadata can be extracted automatically from text captions and restructured with respect to a semantic model. Second, the use of LSI in relation to a domain-specific ontology-based knowledge model enables the combined framework to tolerate ambiguities and variations (incompleteness) of metadata. The use of the ontology-based knowledge model allows the system to find indirectly relevant concepts in image captions and thus leverage these to represent the semantics of images at a higher level. Experimental results show that the proposed framework significantly enhances image retrieval and leads to narrowing of the semantic gap between lower level machinederived and higher level human-understandable conceptualisation

PEDIA: prioritization of exome data by image analysis

Purpose Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. Methods Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. Results The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20–89% and the top 10 accuracy rate by more than 5–99% for the disease-causing gene. Conclusion Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research

Phenotype analyses, e.g. investigating metabolic processes, tissue formation, or organism behavior, are an important element of most biological and medical research activities. Biomedical researchers are making increased use of ontological standards and methods to capture the results of such analyses, with one focus being the comparison and analysis of phenotype information between species. We have generated a cross-species phenotype ontology for human, mouse and zebrafish that contains classes from the Human Phenotype Ontology, Mammalian Phenotype Ontology, and generated classes for zebrafish phenotypes. We also provide up-to-date annotation data connecting human genes to phenotype classes from the generated ontology. We have included the data generation pipeline into our continuous integration system ensuring stable and up-to-date releases. This article describes the data generation process and is intended to help interested researchers access both the phenotype annotation data and the associated cross-species phenotype ontology. The resource described here can be used in sophisticated semantic similarity and gene set enrichment analyses for phenotype data across species. The stable releases of this resource can be obtained from http://purl.obolibrary.org/obo/hp/uberpheno/

Phenotype ontologies and cross-species analysis for translational research

The use of model organisms as tools for the investigation of human genetic variation has significantly and rapidly advanced our understanding of the aetiologies underlying hereditary traits. However, while equivalences in the DNA sequence of two species may be readily inferred through evolutionary models, the identification of equivalence in the phenotypic consequences resulting from comparable genetic variation is far from straightforward, limiting the value of the modelling paradigm. In this review, we provide an overview of the emerging statistical and computational approaches to objectively identify phenotypic equivalence between human and model organisms with examples from the vertebrate models, mouse and zebrafish. Firstly, we discuss enrichment approaches, which deem the most frequent phenotype among the orthologues of a set of genes associated with a common human phenotype as the orthologous phenotype, or phenolog, in the model species. Secondly, we introduce and discuss computational reasoning approaches to identify phenotypic equivalences made possible through the development of intra- and interspecies ontologies. Finally, we consider the particular challenges involved in modelling neuropsychiatric disorders, which illustrate many of the remaining difficulties in developing comprehensive and unequivocal interspecies phenotype mappings

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes