Disclosed herein are classifier models, computer implemented systems, machine learning systems and methods thereof for classifying clinical variants of unknown or uncertain significance into a pathogenicity category using measured phenotype features extracted from phenotype assays of transgenic organism expressing the human clinical variant. Embodiments of the present invention relate generally to methods for generating classifier models using machine learning and use of those classifier models to predict the pathogenicity of a clinical variant for a specific human disease (e.g. genetic disease), assigning a patient clinical variant to a pathogenicity category (e.g. pathogenic or benign) for the specific human disease to determine whether that patient should be followed up with additional, more invasive diagnostic testing, or treatment.

The present disclosure provides a microfluidic device and system for measuring a composite electropharyngeogram (EPG) signal from a pool of multiple nematodes, wherein the composite EPG signal is measured from the pool of nematodes present in a single recording channel connected to two or more integrated electrodes. The microfluidic device includes an inlet port and outlet port directly connected to a single recording channel and two or more electrodes directly connected to the recording channel. The recording channel is configured to hold 10 to 10,000 nematodes.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides a microfluidic device and system for measuring a composite electropharyngeogram (EPG) signal from a pool of multiple nematodes, wherein the composite EPG signal is measured from the pool of nematodes present in a single recording channel connected to two or more integrated electrodes. The microfluidic device includes an inlet port and outlet port directly connected to a single recording channel and two or more electrodes directly connected to the recording channel. The recording channel is configured to hold 10 to 10,000 nematodes.

A method for evaluating biofilm formation on a medical device material in vivo using an invertebrate includes: a step of inserting the medical device material between a hypodermal portion and an intestinal tract of an invertebrate, a step of extracting the medical device material from the invertebrate, and a step of evaluating biofilm formation on the surface of the medical device material; the invertebrate is for use in this evaluation of the biofilm formation.

The present disclosure provides transgenic non-human animal (e.g., nematode) systems for assessing heterologous polygenic or monogenic phenotypes, their variants and drug discovery. The transgenic non-human animals (e.g., nematodes) contain a first heterologous polypeptide coding sequence and a second heterologous polypeptide coding sequence (a plurality of heterologous polypeptide coding sequences), wherein the first and second heterologous polypeptide coding sequences are integrated into the host animal genome, and wherein expression of the first and second heterologous polypeptide coding sequence contribute to the heterologous phenotype. The plurality of heterologous polypeptide coding sequences are interrelated wherein their expression products, directly or indirectly, contribute or lead to an observable phenotype.

This disclosure relates to methods for screening therapeutic agents to treat altered function of a mutated target gene (e.g., clinical variant) as well as reagents for use in the same.

The present invention relates to an animal model for oxidative stress research and use thereof, and more specifically, the present invention can utilize a mutant of RCAT having a regulatory function for an antioxidant stress regulator in Caenorhabditis elegans and a human cell line expressing RCAT as animal and human cell line models for oxidative stress research, using the mutant and the human cell line.

The present disclosure relates to transgenic Caenorhabditis elegans including, in sensory neurons, Channelrhodopsin 2 (ChR2)::Green Fluorescence Protein (GFP) DNA in which the ChR2 gene and the GFP gene are linked, a method of producing the same, a method of regulating the lifespan thereof, and a method of screening an aging regulation candidate by using the same. The present disclosure may also provide an animal model for research into prevention/treatment of aging-related diseases by regulating the lifespan of an animal on a subject level and a method of screening a drug candidate for prevention/treatment of aging-related diseases.

The present invention provides compositions and methods for light-activated cation channel proteins and their uses within cell membranes and subcellular regions. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-activated cation channels to specific cells or defined cell populations. In particular the invention provides millisecond-timescale temporal control of cation channels using moderate light intensities in cells, cell lines, transgenic animals, and humans. The invention provides for optically generating electrical spikes in nerve cells and other excitable cells useful for driving neuronal networks, drug screening, and therapy.