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.

The disclosure describes a method for diagnosing lung cancer in a subject by detecting in a biological sample obtained from that patient a miRNA signature, the presence of which provides an earlier indication of cancer than alternative art-recognized methods, including, but not limited to, low-dose computed tomography (LDCT).

The present patent relates to a method for qualitative identification and quantitative prediction of thyroid hormone disrupting chemicals base on the interaction between thyroid hormone receptor and co-regulators (coactivator and corepressor).The method identifies chemicals as passive antagonists, active antagonists and agonists by means of co-regulator involved molecular dynamics simulations, and predicts the relative disrupting potencies by use of binding free energy, therefore, may be used for screening of thyroid hormone disruptors among environmental pollutants. Upon more comprehensive consideration of the functioning mechanism of thyroid hormone receptor, the present invention is able to sufficiently identify thyroid hormone disruptors as agonists and antagonists, and gives more accurate prediction of the disrupting potency. Further, since nuclear receptors, just as thyroid hormone receptor, are strongly associated with co-regulators, the method may be expanded to the screening of nuclear receptor mediated endocrine disruptors.

The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.

Disclosed herein are methods for predicting immunogenicity of a candidate peptide. The method comprises obtaining a three-dimensional candidate structural representation of the candidate peptide bound to an antigen presenting molecule; obtaining a plurality of candidate measurements; and predicting, with an electronic processor, the immunogenicity of the candidate peptide based upon the plurality of candidate measurements. Further disclosed herein are methods for producing vaccines. The method for producing a vaccine comprises predicting immunogenicity of one or more candidate peptides using the methods described herein, and producing a vaccine comprising one or more peptides predicted to be immunogenic.

Disclosed herein are methods for predicting immunogenicity of a candidate peptide. The method comprises obtaining a three-dimensional candidate structural representation of the candidate peptide bound to an antigen presenting molecule; obtaining a plurality of candidate measurements; and predicting, with an electronic processor, the immunogenicity of the candidate peptide based upon the plurality of candidate measurements. Further disclosed herein are methods for producing vaccines. The method for producing a vaccine comprises predicting immunogenicity of one or more candidate peptides using the methods described herein, and producing a vaccine comprising one or more peptides predicted to be immunogenic.

A three-dimensional image reconstruction method associated with the present invention comprises the steps of: obtaining a first transmission electron microscope image of a sample containing the membrane proteins present within a lipid membrane, the image having been taken by illuminating an electron beam on the sample from a direction tilted relative to a line normal to the membrane surface of the lipid membrane (step S10); obtaining a second transmission electron microscope image of the sample taken by illuminating the electron beam on the sample perpendicularly to the membrane surface of the lipid membrane (step S12); identifying orientations of the membrane proteins of the first transmission electron microscope image on a basis of the second transmission electron microscope image (step S14); and analyzing a three-dimensional structure of the membrane proteins from the first transmission electron microscope image on a basis of information about the identified orientations of the membrane proteins (step S18).

The present invention relates to a method of predicting the propensity of tripeptides to from aggregates in solution. The present invention also provides tripeptides which are able to form aggregates in solution, as well as uses thereof. The present invention also provides nanostructures formed by self-aggregation of tripeptides of the present invention. The present invention also provides pH responsive aggregates as well as methods of screening for the ability of a tripeptide to form a pH dependent aggregate or gel.

A protein composition including TorsinA or TorsinA mutant, LULL1, and a nanobody obtained by immunization using TorsinA and LULL1 is used to grow complex crystals, and three dimensional structures are determined using x-ray data of the crystals. A creening platform is built based on the determined three dimensional structures for designing a drug lead to cure dystonia.

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.