Abstract: After DNA fragments are sequenced and mapped to a reference, various hypotheses for the sequences in a variant region can be scored to find which sequence hypotheses are more likely. A hypothesis can include a specific variable fraction for the plurality of alleles that comprise the sequence hypothesis in the region. A likelihood of each hypothesis can be determined using a probability that accounts for the fraction of the alleles specified in the respective sequence hypothesis. Thus, other hypotheses besides standard homozygous and equal heterozygous (i.e., one chromosome with A and one with B in a cell) can be explored by explicitly including the variable fractions of the alleles as a parameter in the optimization. Also, a variant score can be determined for a variant relative to a reference. The variant score can be used to determine a variant calibrated score indicating a likelihood that the variant call is correct.

Abstract: A thermally aware design automation suite integrates system-level thermal awareness into design of semiconductor chips, performing fine-grain static and/or transient thermal simulations of the chips based on thermal models and boundary conditions. The thermal simulations are performed in accordance with one or more grids, with boundaries and/or resolutions being determined by adaptive and/or hierarchical multi-dimensional techniques. The adaptive grid techniques include material-boundary, rate-of-change, and convergence-information heuristics. For example, a finer grid is used in a region having higher temperature gradients compared to a region having lower temperature gradients. The hierarchical grid techniques are based on critical, intermediate, and boundary regions specified manually or automatically, each region having a respective grid resolution.

Abstract: Methods, apparatuses, and systems for identification of junctions (e.g., resulting from large-scale rearrangements) of a sequenced genome with respect to a human genome reference sequence is provided. For example, false positives can be distinguished from actual junctions. Such false positives can result from many sources, including mismapping, chimeric reactions among the DNA of a sample, and problems with the reference genome. As part of the filtering processes, a base pair resolution (or near base pair resolution) of a junction can be provided. In various implementations, junctions can be identified using discordant mate pairs and/or using a statistical analysis of the length distributions of fragments for local regions of the sample genome. Clinically significant junctions can also be identified so that further analysis can be focused on genomic regions that may have more of an impact on the health of a patient.

Abstract: Transient thermal simulation of semiconductor chips uses region-wise variable spatial grids and variable temporal intervals, enabling spatio-temporal thermal analysis of semiconductor chips. Temperature rates of change across a die and/or package of an integrated circuit are computed and tracked versus time. Critical time interval(s) for temperature evaluation are determined. Temperatures of elements, components, devices, and interconnects are updated based on a 3D full chip temperature analysis. Respective power dissipations are updated, as a function of the temperatures, with an automated interface to one or more circuit simulation tools. Subsequently new temperatures are determined as a function of the power dissipations. User definable control and observation parameters enable flexible and efficient transient thermal analysis. The parameters relate to power sources, monitoring, reporting, error tolerances, and output snapshots.

Abstract: Embodiments for calling variations in a sample polynucleotide sequence compared to a reference polynucleotide sequence are provided. Aspects of the embodiments include executing an application on at least one computer that locates local areas in the reference polynucleotide sequence where a likelihood exists that one or more bases of the sample polynucleotide sequence are changed from corresponding bases in the reference polynucleotide sequence, where the likelihood is determined at least in part based on mapped mated reads of the sample polynucleotide sequence; generating at least one sequence hypothesis for each of the local areas, and optimizing the at least one sequence hypothesis for at least a portion of the local areas to find one or more optimized sequence hypotheses of high probability for the local areas; and analyzing the optimized sequence hypotheses to identify a series of variation calls in the sample polynucleotide sequence.

Abstract: A new approach to identifying binding conformations of chemical fragments and biological molecules is presented, in which fragment poses are explored in a systematic fashion. In an embodiment, for each pose, a fast computation is performed of the fragment interaction with the biological molecule using interpolation on a grid. Once the energies of fragment poses are computed, thermodynamical quantities such as binding affinity, binding enthalpy, and binding entropy are computed by direct sum over fragment poses. Using the present invention, it is possible to navigate fragment configuration space to identify separate binding modes. The present invention can be used to scan an entire biological molecule to identify possible binding pockets, or it can be used for localized explorations limited to interesting areas of known binding pockets.

Abstract: A thermally aware design automation suite integrates system-level thermal awareness into design of semiconductor chips, performing fine-grain static and/or transient thermal simulations of the chips based on thermal models and boundary conditions. The thermal simulations are performed in accordance with one or more grids, with boundaries and/or resolutions being determined by adaptive and/or hierarchical multi-dimensional techniques. The adaptive grid techniques include material-boundary, rate-of-change, and convergence-information heuristics. For example, a finer grid is used in a region having higher temperature gradients compared to a region having lower temperature gradients. The hierarchical grid techniques are based on critical, intermediate, and boundary regions specified manually or automatically, each region having a respective grid resolution.

Abstract: A new approach to identifying binding conformations of chemical fragments and biological molecules is presented, in which fragment poses are explored in a systematic fashion. In an embodiment, for each pose, a fast computation is performed of the fragment interaction with the biological molecule using interpolation on a grid. Once the energies of fragment poses are computed, thermodynamical quantities such as binding affinity, binding enthalpy, and binding entropy are computed by direct sum over fragment poses. Using the present invention, it is possible to navigate fragment configuration space to identify separate binding modes. The present invention can be used to scan an entire biological molecule to identify possible binding pockets, or it can be used for localized explorations limited to interesting areas of known binding pockets.