GPCR-fusion partner proteins comprising G protein coupled receptors (GPCRs) of GPCRs and fusion partners such as rubredoxin, cytochrome b562 RIL (Bril, bRIL, BRIL), T4 lysozyme C-terminal fragment (C-term-T4L), flavodoxin, or xylanase either substituted for some or all of the third intracellular loop of the GPCR between the fifth and sixth helix of the GPCR are described or attached to an terminus or C terminus of the GPCR. GPCR-fusion partner proteins in crystalline form, optionally of a quality suitable for x-ray crystallographic structure determination of the GPCR, are described. Methods of using fusion partners in GPCR-fusion partner proteins to support crystallization of GPCR-fusion partner proteins for x-ray crystallographic structure determination of the GPCR, are described. Methods of identifying other suitable fusion partners through screening of protein data banks are also described.

Bacteriophage Insensitive Mutants (BIMs) of three Streptococcus thermophilus parent strains were generated and characterized for phage sensitivity, sedimentation rate, cell chain length, phage adsorption and CRISPR loci alterations. Several BIMs showed an altered sedimentation phenotype as well as an increase cell chain length, reduced phage sensitivity, reduced phage adsorption and 100% identity in three CRISPR loci. The results show that the derived BIMs have become phage-resistant through a mechanism other than CRISPR.

Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter. In some implementations, information from fragments of different sizes are used to evaluate copy number variations. In some implementations, one or more t-statistics obtained from coverage information of the sequence of interest is used to evaluate copy number variations. In some implementations, one or more fetal fraction estimates are combined with one or more t-statistics to determine copy number variations.

A computer-implemented method of preparing a set of differentially informative methylated positions (DIMPs) or differentially informative methylated regions (DIMRs) from a sample methylome of an animal or plant having a phenotypic characteristic different from a wild-type of the same species of animal or plant, and the characteristic is associate with differences in methylation of the genome, comprises: providing a computer with the sample methylome, and a reference methylome of the wild-type of the same species of animal or plant; calculating with the computer a divergence between a plurality of cytosine positions of the sample methylome and the reference methylome; and selecting with the computer a set of DIMPs or DIMRs. Each DIMP or DIMR is selected based on an approximation of the energy required to produce the divergence between methylation levels of the plurality of cytosine positions of the sample methylome as compared to the wild-type methylome.

Generation of biomolecule sequence coevolution data structures, matrices, scores, and sectors are described. Generally, the generated coevolution data removes covariant noise due to phylogenetic drift and can reveal coevolution of residue positions in multiple phylogenetic distances. Scores can be built upon the data structures and matrices to reveal sectors of residue positions that function and evolve together. Furthermore, the coevolution data structures, matrices, scores, and sectors can be used to predict structure or function of residue variants.

This disclosure provides methods for determining relative abundance of one or more non-host species in a sample from a host. Also provided are methods involving addition of known concentrations of synthetic nucleic acids to a sample and performing sequencing assays to identify non-host species such as pathogens. Also provided are methods of tracking samples, tracking reagents, and tracking diversity loss in sequencing assays.

The invention relates to methods and systems for sequencing and constructing a high resolution physical map of a polynucleotide. In accordance with the invention, nucleotide sequences are determined at the ends of restriction fragments produced by a plurality of digestions with a plurality of combinations of restriction endonucleases so that a pair of nucleotide sequences is obtained for each restriction fragment. A physical map of the polynucleotide is constructed by ordering the pairs of sequences by matching the identical sequences among the pairs.

Disclosed herein is a method and an arrangement for the control of measuring systems such as a mass spectrometer or nuclear magnetic resonance (NMR) instrument, the control being based on an online data analysis of the current measurements. Depending on the measurement experiment, the combined result of the data analysis can have either a direct influence on the next measurement or result in a dynamically organized sequence of measurements. The measuring systems may be controlled by establishing a database that comprises information on the objects to be measured, the measurement data which can be detected during the measurement experiments using the measuring systems, and information regarding the relationships between or among items of the measurement data.

The invention provides methods for comparing one set of genetic sequences to another without discarding any information within either set. A set of genetic sequences is represented using a directed acyclic graph (DAG) avoiding any unwarranted reduction to a linear data structure. The invention provides a way to align one sequence DAG to another to produce an alignment that can itself be stored as a DAG. DAG-to-DAG alignment is a natural choice wherever a set of genomic information consisting of more than one string needs to be compared to any non-linear reference. For example, a subpopulation DAG could be compared to a population DAG in order to compare the genetic features of that subpopulation to those of the population.

Methods and systems for ordering assays which detect SNPs or gene expression are provided. The methods use PCR and RT-PCR procedures. Collections of stock assays are assembled using pre- and post-manufacturing quality control procedures and made available to consumers via the Internet. In addition, custom assays are prepared upon order from the consumer and these assays are also prepared using pre- and post-manufacturing quality control procedures. The assays are then delivered to the consumer.