Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional network network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional neural network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: Systems, computer-implemented methods, and non-transitory computer readable media are provided for sharing medical data. The disclosed systems may be configured to create a first workgroup having a first knowledgebase. This first knowledgebase may be federated with a common knowledgebase, and with a second knowledgebase of a second workgroup. At least one of the first knowledgebase, common knowledgebase, and second knowledgebase may be configured to store data items comprising associations, signs, and evidence. The signs may comprise measurements and contexts, and the associations may describe the relationships between the measurements and contexts. The evidence may support these associations. The disclosed systems may be configured to receive a request from a user in the first workgroup, retrieve matching data items, and optionally then output to the user at least some of the retrieved matching data items. The request may comprise at least one of a first association and a first measurement.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional neural network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: Systems, computer-implemented methods, and non-transitory computer readable media are provided for sharing medical data. The disclosed systems may be configured to create a first workgroup having a first knowledgebase. This first knowledgebase may be federated with a common knowledgebase, and with a second knowledgebase of a second workgroup. At least one of the first knowledgebase, common knowledgebase, and second knowledgebase may be configured to store data items comprising associations, signs, and evidence. The signs may comprise measurements and contexts, and the associations may describe the relationships between the measurements and contexts. The evidence may support these associations. The disclosed systems may be configured to receive a request from a user in the first workgroup, retrieve matching data items, and optionally then output to the user at least some of the retrieved matching data items. The request may comprise at least one of a first association and a first measurement.

Abstract: Derivation and use of pathogenicity scores for gene variants are described herein. Applications, uses, and variations of the pathogenicity scoring process include, but are not limited to, the derivation and use of thresholds to characterize a variant as pathogenic or benign, the estimation of selection effects associated with a gene variant, the estimation of genetic disease prevalence using pathogenicity scores, and the recalibration of methods used to assess pathogenicity scores.

Abstract: Derivation and use of pathogenicity scores for gene variants are described herein. Applications, uses, and variations of the pathogenicity scoring process include, but are not limited to, the derivation and use of thresholds to characterize a variant as pathogenic or benign, the estimation of selection effects associated with a gene variant, the estimation of genetic disease prevalence using pathogenicity scores, and the recalibration of methods used to assess pathogenicity scores.

Abstract: Systems, computer-implemented methods, and non-transitory computer readable media are provided for sharing medical data. The disclosed systems may be configured to create a first workgroup having a first knowledgebase. This first knowledgebase may be federated with a common knowledgebase, and with a second knowledgebase of a second workgroup. At least one of the first knowledgebase, common knowledgebase, and second knowledgebase may be configured to store data items comprising associations, signs, and evidence. The signs may comprise measurements and contexts, and the associations may describe the relationships between the measurements and contexts. The evidence may support these associations. The disclosed systems may be configured to receive a request from a user in the first workgroup, retrieve matching data items, and optionally then output to the user at least some of the retrieved matching data items. The request may comprise at least one of a first association and a first measurement.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional neural network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: The technology disclosed presents a deep learning-based framework, which identifies sequence patterns that cause sequence-specific errors (SSEs). Systems and methods train a variant filter on large-scale variant data to learn causal dependencies between sequence patterns and false variant calls. The variant filter has a hierarchical structure built on deep neural networks such as convolutional neural networks and fully-connected neural networks. Systems and methods implement a simulation that uses the variant filter to test known sequence patterns for their effect on variant filtering. The premise of the simulation is as follows: when a pair of a repeat pattern under test and a called variant is fed to the variant filter as part of a simulated input sequence and the variant filter classifies the called variant as a false variant call, then the repeat pattern is considered to have caused the false variant call and identified as SSE-causing.

Abstract: Systems, computer-implemented methods, and non-transitory computer readable media are provided for sharing medical data. The disclosed systems may be configured to create a first workgroup having a first knowledgebase. This first knowledgebase may be federated with a common knowledgebase, and with a second knowledgebase of a second workgroup. At least one of the first knowledgebase, common knowledgebase, and second knowledgebase may be configured to store data items comprising associations, signs, and evidence. The signs may comprise measurements and contexts, and the associations may describe the relationships between the measurements and contexts. The evidence may support these associations. The disclosed systems may be configured to receive a request from a user in the first workgroup, retrieve matching data items, and optionally then output to the user at least some of the retrieved matching data items. The request may comprise at least one of a first association and a first measurement.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional network network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional neutral network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: The technology disclosed includes systems and methods to reduce overfitting of neural network-implemented models that process sequences of amino acids and accompanying position frequency matrices. The system generates supplemental training example sequence pairs, labelled benign, that include a start location, through a target amino acid location, to an end location. A supplemental sequence pair supplements a pathogenic or benign missense training example sequence pair. It has identical amino acids in a reference and an alternate sequence of amino acids. The system includes logic to input with each supplemental sequence pair a supplemental training position frequency matrix (PFM) that is identical to the PFM of the benign or pathogenic missense at the matching start and end location. The system includes logic to attenuate the training influence of the training PFMs during training the neural network-implemented model by including supplemental training example PFMs in the training data.

Abstract: We disclose computational models that alleviate the effects of human ascertainment biases in curated pathogenic non-coding variant databases by generating pathogenicity scores for variants occurring in the promoter regions (referred to herein as promoter single nucleotide variants (pSNVs)). We train deep learning networks (referred to herein as pathogenicity classifiers) using a semi-supervised approach to discriminate between a set of labeled benign variants and an unlabeled set of variants that were matched to remove biases.

Abstract: Systems, computer-implemented methods, and non-transitory computer readable media are provided for determining related ontological data. The disclosed systems may be configured to receive a first ontology and a second ontology, the first ontology and the second ontology comprising hierarchically organized ontological data. The disclosed systems may also be configured to receive an indication that a first ontological datum in the first ontology is equivalent to a second ontological datum in the second ontology, and a query for ontological data related to a third ontological datum subordinate to the first ontological datum. The disclosed systems may be configured to determine a first semantic distance between the third ontological datum and a fourth ontological datum in the second ontology satisfies a semantic distance criterion, and output the fourth ontological datum based on the determination that the first semantic distance satisfies the semantic distance criterion.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional network network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: The technology disclosed includes systems and methods to reduce overfitting of neural network-implemented models that process sequences of amino acids and accompanying position frequency matrices. The system generates supplemental training example sequence pairs, labelled benign, that include a start location, through a target amino acid location, to an end location. A supplemental sequence pair supplements a pathogenic or benign missense training example sequence pair. It has identical amino acids in a reference and an alternate sequence of amino acids. The system includes logic to input with each supplemental sequence pair a supplemental training position frequency matrix (PFM) that is identical to the PFM of the benign or pathogenic missense at the matching start and end location. The system includes logic to attenuate the training influence of the training PFMs during training the neural network-implemented model by including supplemental training example PFMs in the training data.