The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.

The present invention relates to methods for evaluating the probability that a patient's diagnosis may be treated with a particular clinical regimen or therapy.

The invention is directed to methods and metric suitable for use in modulating the expression of a polypeptide encoded by a nucleic acid sequence. In certain aspects, the invention also relates to methods for introducing modifications in a polypeptide, for example through substitution of one or more nucleic acids in an untranslated sequence or in a coding sequence of a nucleic acid sequence encoding a polypeptide to increase the expression of the polypeptide.

The presently disclosed subject matter provides a free-energy based model of translation elongation to predict and optimize heterologous gene expression. The model and software allow for the prediction and optimization of genes for increased or decreased protein yield and for increased or decreased protein aggregation.

Systems and methods described herein include those for the continual modification of intestinal microbes. Described herein are systems including sampling devices, analysis devices, computational devices and user interface devices as well as methods for the use of such devices in combination.

A method of identifying co-expressed coding and noncoding genes is disclosed. The method may include receiving genetic sequences, mapping the genetic sequences to known coding and noncoding genes, correlating the mapped genes, and generating a co-expression network. A system for generating a co-expression network and providing the co-expression network to a user on a display is disclosed. The system may include a memory, one or more processors, one or more databases, and a display.

A method of identifying a promising cellular antiviral or bacterial toxin drug target is described including: 1) providing a plurality of potential antiviral or bacterial toxin drug targets; 2) generating an interactome including the potential drug targets using a systems-biology computational method; and 3) analyzing the interactome to identify one or more promising antiviral or bacterial toxin drug targets. New indications for older drugs identified using this method are also described.

A genotyping device includes a representative value calculator, a first labeler, a model creator, a second labeler. The representative value calculator calculates a representative value for each of one or more clusters with respect to each of a plurality of SNPs. The representative value being calculated based on signal intensities of specimens included in each of the clusters. The first labeler assigns genotypes to clusters of an SNP pertaining to three clusters among the SNPs on basis of the representative values of the clusters. The model creator creates a model indicative of a relationship between the genotypes of the clusters of the SNP pertaining to the three clusters among the SNPs and the representative values of the clusters. The second labeler assigns genotypes to clusters of an SNP pertaining to one or two clusters among the SNPs on basis of the representative values of the clusters and the model.

Methods may include defining operational parameters for an initial composition design; generating an initial composition design from the defined operational parameters; predicting the performance of the initial composition design using a statistical model; comparing the performance of the initial composition design with the operational parameters; optimizing the initial composition design according to the defined operational parameters; and outputting a final composition design. Methods may also include defining operational parameters for an initial composition design for a wellbore fluid; generating an initial composition design from the defined operational parameters; predicting the performance of the initial composition design using a statistical model; comparing the performance of the initial composition design with the operational parameters; optimizing the initial composition design according to the defined operational parameters; and outputting a final composition design.

Described are mathematical models and method, e.g., computer-implemented methods, for predicting tumor sensitivity to radiation therapy, which can be used, e.g., for selecting a treatment for a subject who has a tumor.