Genetic resistance prediction against antimicrobial drugs in microorganism using structural changes in the genome

The invention relates to a method of determining an infection of a patient with at least one microorganism, particularly a bacterial microorganism, potentially resistant to antimicrobial drug treatment, a method of selecting a treatment of a patient suffering from an infection with at least one microorganism, particularly bacterial microorganism, and a method of determining structural changes of the genome of the microorganism, particularly bacterial microorganism, comprising at least one gene, as well as computer program products used in these methods.

In a method of compressing a similarity network, the similarity network has nodes with a plurality of repetitions of characters sequences and a plurality of edges. Each edge connects a pair of the nodes based on a first similarity threshold. The method includes clustering of the nodes according to a second similarity threshold, where the second similarity threshold is higher than the first similarity threshold.

Methods predict candidate epitopes in a protein by: providing a conformational sampling engine; obtaining a model of a protein suitable for use with the conformational sampling engine and comprising a native structure; applying a collective coordinate bias to the protein model, the collective coordinate bias causing the conformational sampling engine to in turn force the protein model to at least partially unfold from its native structure to an updated structure, wherein the collective coordinate bias is applied globally to at least a substantial portion of the protein model and is impartial as to where, within the substantial portion of the protein model, unfolding occurs; and analyzing the updated structure to identify one or more candidate epitopes, where the one or more candidate epitopes exhibit indicia of localized unfolding.

The invention relates, in part, to systems and methods for scoring a sample containing tumor tissue from a cancer patient. The score obtained from these methods can be indicative of a likelihood that a patient may respond positively to immunotherapy. The invention also relates, in part, to methods of deriving a value for % biomarker positivity (PBP) for all cells or optionally, one or more subsets thereof, present in a field of view of a tissue sample from a cancer patient. The values for PBP can be indicative of a patient's response to immunotherapy.

The present invention relates to a method for producing a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having a non-human-derived CDR3 amino acid sequence embedded in essentially human framework sequences, as well as to a population of nucleic acids and a population of proteins relates thereto and uses thereof.

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimized Staphylococcus aureus CRISPR-Cas enzyme systems.

The invention relates to amino acid sequence variants of a lipase with improved activity for catalyzing synthesis reactions and methods of preparing the variants. The methods include predicting amino acid sites for change based on computational models of the protein structure in non-aqueous conditions, and expressing the protein in a prokaryotic host for subsequent purification and use. The enzyme sequence variants described have a three to nine-fold improvement in synthesis activity over the parent protein sequence.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

The invention describes an explicit solvent all-atom molecular dynamics methodology (SILCS: Site Identification by Ligand Competitive Saturation) that uses small aliphatic and aromatic molecules plus water molecules to map the affinity pattern of a large molecule for hydrophobic groups, aromatic groups, hydrogen bond donors, and hydrogen bond acceptors. By simultaneously incorporating ligands representative of all these functionalities, the method is an in silico free energy-based competition assay that generates three-dimensional probability maps of fragment binding (FragMaps) indicating favorable fragment:large molecule interactions. The FragMaps may be used to qualitatively inform the design of small-molecule ligands or as scoring grids for high-throughput in silico docking that incorporates both an atomic-level description of solvation and the large molecule's flexibility.