Methods for selecting a cancer patient for immunotherapy comprise establishing a total passenger gene mutation burden from a tumor of a cancer patient, generating a background distribution for the mutational burden of the tumor, normalizing the total passenger gene mutation burden against the background distribution, and categorizing the cancer patient as an immunotherapy responder when the total passenger gene mutation burden is greater than the mean of the background distribution. When the cancer patient is an immunotherapy responder, the patient may be administered an immunotherapy regimen that comprises activation/inhibition of T cell receptors that promote T cell activation and/or prolong immune cytolytic activities.

Single cell ribonucleic acid sequencing data has provided numerous avenues to monitor and study organism more thoroughly at a cellular level, including spatial arrangement of cells. An approach to predicting cellular immune response based on cellular spatial features may be presented herein. The approach may include utilizing ribonucleic acid sequence data for a single cell (“scRNA-seq”) or cell from a tissue. The approach may also include extracting spatial features of the single cell using the scRNA-seq data including cell-to-cell interactions and relative distance between cells. The approach may include predicting an immune response of a cell or cells based on the extracted spatial features.

Single cell ribonucleic acid sequencing data has provided numerous avenues to monitor and study organism more thoroughly at a cellular level, including spatial arrangement of cells. An approach to predicting cellular immune response based on cellular spatial features may be presented herein. The approach may include utilizing ribonucleic acid sequence data for a single cell (“scRNA-seq”) or cell from a tissue. The approach may also include extracting spatial features of the single cell using the scRNA-seq data including cell-to-cell interactions and relative distance between cells. The approach may include predicting an immune response of a cell or cells based on the extracted spatial features.

An analytic method for improving the efficiency in identifying protein molecular effect information using low resolution x-ray crystallography, by selecting and imaging a protein sample with low resolution x-ray crystallography and assaying the data thus generated as to local ligand strain energy value, followed by calculating a real-space difference density Z for each element and compiling ZDD data therefrom, followed by determining the true protomer/tautomer state of the protein sample by calculating Score.sub.i according to the following equation so that the highest Score.sub.i signifies the molecular effect information:
Score.sub.i={((ZDD.sub.i−μ.sub.ZDD)/σ.sub.ZDD)+((SE.sub.i−σ.sub.SE)/σ.sub.SE)}.

An analytic method for improving the efficiency in identifying protein molecular effect information using low resolution x-ray crystallography, by selecting and imaging a protein sample with low resolution x-ray crystallography and assaying the data thus generated as to local ligand strain energy value, followed by calculating a real-space difference density Z for each element and compiling ZDD data therefrom, followed by determining the true protomer/tautomer state of the protein sample by calculating Score.sub.i according to the following equation so that the highest Score.sub.i signifies the molecular effect information:
Score.sub.i={((ZDD.sub.i−μ.sub.ZDD)/σ.sub.ZDD)+((SE.sub.i−σ.sub.SE)/σ.sub.SE)}.

Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.

Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.

The present invention relates to compounds of the general formula (I) having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. ##STR00001##

Disclosed herein in are methods and systems for determining genetic variants (e.g., copy number variation) in a polynucleotide sample. A method for determining copy number variations includes tagging double-stranded polynucleotides with duplex tags, sequencing polynucleotides from the sample and estimating total number of polynucleotides mapping to selected genetic loci. The estimate of total number of polynucleotides can involve estimating the number of double-stranded polynucleotides in the original sample for which no sequence reads are generated. This number can be generated using the number of polynucleotides for which reads for both complementary strands are detected and reads for which only one of the two complementary strands is detected.

Methods for the top-down design of nucleic acid nanostructures of arbitrary geometry based on target shape of spherical or non-spherical topology are described. The methods facilitate 3D molecular programming of lipids, proteins, sugars, and RNAs based on a DNA scaffold of arbitrary 2D or 3D shape. Geometric objects are rendered as node-edge networks of parallel nucleic acid duplexes, and a nucleic acid scaffold routed throughout the network using a spanning tree formula. Nucleic acid nanostructures produced according to top-down design methods are also described. In some embodiments, the nanostructures include single-stranded nucleic acid scaffold, DX crossovers, and staple strands. In other embodiments, the nanostructures include single-stranded nucleic acid scaffold, PX crossovers and no staples. Modified nanostructures include chemically modified nucleotides and conjugated to other molecules are described.