Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.

Described are techniques for determining population structure from identity-by-descent (IBD) of individuals. The techniques may be used to predict that an individual belongs to zero, one or more of a number of communities identified within an IBD network. Additional data may be used to annotate the communities with birth location, surname, and ethnicity information. In turn, these data may be used to provide to an individual a prediction of membership to zero, one or more communities, accompanied by a summary of the information annotated to those communities.

Described are techniques for determining population structure from identity-by-descent (IBD) of individuals. The techniques may be used to predict that an individual belongs to zero, one or more of a number of communities identified within an IBD network. Additional data may be used to annotate the communities with birth location, surname, and ethnicity information. In turn, these data may be used to provide to an individual a prediction of membership to zero, one or more communities, accompanied by a summary of the information annotated to those communities.

The invention provides systems and methods for discovering candidate therapies for genetic conditions and also for screening those therapies in vitro for evidence of neurotoxicity. Where a medical condition is a consequence of a genetic target such as a mutated gene, the disclosure provides in silico methods to generate lists of candidate sequences for antisense oligonucleotides (ASOs) that will potentially bind to the gene or transcripts from the gene in vivo and treat the associated condition by restoring a healthy phenotype of gene expression. The invention provides in vitro methods for screening candidate ASO sequences for symptoms of neurotoxicity in vivo. For example, candidate sequences that are output by the in silico analytical pipeline can be synthesized and assayed against live cells in vitro.

The invention provides systems and methods for discovering candidate therapies for genetic conditions and also for screening those therapies in vitro for evidence of neurotoxicity. Where a medical condition is a consequence of a genetic target such as a mutated gene, the disclosure provides in silico methods to generate lists of candidate sequences for antisense oligonucleotides (ASOs) that will potentially bind to the gene or transcripts from the gene in vivo and treat the associated condition by restoring a healthy phenotype of gene expression. The invention provides in vitro methods for screening candidate ASO sequences for symptoms of neurotoxicity in vivo. For example, candidate sequences that are output by the in silico analytical pipeline can be synthesized and assayed against live cells in vitro.

The invention utilizes virtual screening strategy to seek for current market drugs as anti-schizophrenia therapy drug repurposing. Drug repurposing strategy finds new uses other than the original medical indications of existing drugs. Finding new indications for such drugs will benefit patients who are in needs for a potential new therapy sooner since known drugs are usually with acceptable safety and pharmacokinetic profiles. In this study, repurposing marketed drugs for DAAO inhibitor as new schizophrenia therapy was performed with virtual screening on marketed drugs and its metabolites. The identified and available drugs and compounds were further confirmed with in vitro DAAO enzymatic inhibitory assay.

The invention utilizes virtual screening strategy to seek for current market drugs as anti-schizophrenia therapy drug repurposing. Drug repurposing strategy finds new uses other than the original medical indications of existing drugs. Finding new indications for such drugs will benefit patients who are in needs for a potential new therapy sooner since known drugs are usually with acceptable safety and pharmacokinetic profiles. In this study, repurposing marketed drugs for DAAO inhibitor as new schizophrenia therapy was performed with virtual screening on marketed drugs and its metabolites. The identified and available drugs and compounds were further confirmed with in vitro DAAO enzymatic inhibitory assay.

The present disclosure discusses a system and method for disease module detection. More particularly, a protein network and list of seed proteins are provided to the system. The system iteratively selects one or more candidate proteins for inclusion in the list of seed proteins. The system calculates a connectivity factor for each of the connections of the candidate proteins to proteins listed as seed proteins. Responsive to the calculated connectivity factors the system adds one or more of the candidate proteins to list of seed proteins. At the end of the iterative process the list of seed proteins can be indicative of the disease module.

The present disclosure discusses a system and method for disease module detection. More particularly, a protein network and list of seed proteins are provided to the system. The system iteratively selects one or more candidate proteins for inclusion in the list of seed proteins. The system calculates a connectivity factor for each of the connections of the candidate proteins to proteins listed as seed proteins. Responsive to the calculated connectivity factors the system adds one or more of the candidate proteins to list of seed proteins. At the end of the iterative process the list of seed proteins can be indicative of the disease module.

The invention relates to improved strategies, compositions, and methods for producing neoplasia vaccines and for their use in methods of treating cancer in a patient. In aspects, a method of treating cancer comprises: (a) administering an effective amount of one or more of the instantly-disclosed peptides or polypeptides comprising one or more identified shared neo-epitopes (including peptides or polypeptide comprising one or more peptides or polypeptides from Table A, B, and/or C and/or fragments and variants thereof); and subsequently (b) administering an effective amount of one or more of the instantly-disclosed subject-specific peptides or polypeptides comprising one or more identified subject-specific neo-epitopes. The peptides or polypeptides administered in step (a) and in step (b) are designed to exclude neo-epitopes that are known or determined (e.g. predicted) to engage regulatory T cells and/or other detrimental T cells (including T cells with potential host cross-reactivity and/or anergic T cells).