Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.

Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.

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.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

Methods of evaluating or providing a clonal profile of a subject interval, e.g., a subgenomic interval, or an expressed subgenomic interval (or of a cell containing the same), in a subject, are disclosed.

A method of correcting an expression level(s) of a target small RNA(s) for comparative analysis of the expression level(s) in a plurality of samples includes adding at least one kind of standard substance to each of the plurality of samples, extracting nucleic acids from each sample to obtain a nucleic acid sample; measuring the amounts of the target small RNA(s) and the standard substance(s) present in each extracted nucleic acid sample; obtaining a representative value from the measured value(s) of the amount(s) of the standard substance(s) extracted; obtaining the difference or the ratio between a reference value arbitrarily set in connection with the amount(s) of the standard substance(s) extracted and the representative value of the standard substance(s) obtained for each sample; and correcting the expression level(s) of the target small RNA(s).

A method, computer program product, and system for identifying a surface area size of a biosensing structure, for use in a biosensor device, based on a plurality of nucleotides structures under test. A first set of properties are determined comprising: reaction coordinate values, and potential of mean force (PMF) values, for the plurality of nucleotide structures based on a first set of testing conditions comprising a first surface area material, a first surface area pattern, and a first surface area size. A second set of properties is determined comprising reaction coordinate values, and PMF values, for the plurality of nucleotide structures based on a second set of testing conditions comprising a second surface area material, a second surface area pattern, a second surface area size, or a combination thereof and a target population of nucleotide structures among the plurality of nucleotide structures are identified.

Methods for identifying and classifying differences between biological samples are based on replication timing (RT) data. By comparing RT data for a test sample(s) to RT data for already characterized samples, one can identify differences and profile any new cell type or disease. These new methods allow for the detection of all the changes between distinct samples, many of which would escape detection by previous methods that discard any features showing any intra-sample variation.

Methods and systems for constructing a gene expression signature representative of a number of biological conditions, systems and methods for determining functional relationships between a skin-active agent and skin conditions of interest, and methods and systems for identifying skin-active agents with broad spectrum activity are provided.