Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.

A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.

A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.

A method is provided for determining, the presence and concentration of an analyte by contacting the sample with a solution comprising: magnetic beads, a capture probe capable of binding the analyte, a reporter probe and cellulose, whereby, if the analyte is present, an MB-analyte-reporter-cellulase sandwich is formed; and then contacting the solution comprising the sandwich with an electrode covered with an electrically insulating layer comprising or consisting of cellulose and/or a cellulose derivative, wherein the MB-analyte-reporter-cellulase sandwich leads to degradation of the insulating layer thereby causing a measurable change in electrical properties at the electrode surface, wherein the change in electrical properties is a function of the amount of analyte in the sample. Devices and biosensor applying the method are also provided.

A method is provided for determining, the presence and concentration of an analyte by contacting the sample with a solution comprising: magnetic beads, a capture probe capable of binding the analyte, a reporter probe and cellulose, whereby, if the analyte is present, an MB-analyte-reporter-cellulase sandwich is formed; and then contacting the solution comprising the sandwich with an electrode covered with an electrically insulating layer comprising or consisting of cellulose and/or a cellulose derivative, wherein the MB-analyte-reporter-cellulase sandwich leads to degradation of the insulating layer thereby causing a measurable change in electrical properties at the electrode surface, wherein the change in electrical properties is a function of the amount of analyte in the sample. Devices and biosensor applying the method are also provided.

Provided herein is a nucleotide cassette comprising an inducible promoter, a nucleotide sequence that corresponds to at least one single stranded RNA diagnostic target, a nucleotide sequence that encodes artemin, a molecular switch and a nucleotide sequence that encodes a DNAse enzyme and is under control of the molecular switch, wherein the single stranded RNA diagnostic target is a sequence detected by a molecular diagnostic assay. In some embodiments the nucleotide cassette can be used to obtain an RNA expression product. Also provided are vectors and cells comprising the nucleotide cassette or the RNA expression product thereof. The nucleotide cassette can further be used to obtain a diagnostic control composition comprising a non-pathogenic recombinant bacterium having a modified genetic content comprising the nucleotide cassette and to methods of producing such recombinant bacteria.

Provided herein is a nucleotide cassette comprising an inducible promoter, a nucleotide sequence that corresponds to at least one single stranded RNA diagnostic target, a nucleotide sequence that encodes artemin, a molecular switch and a nucleotide sequence that encodes a DNAse enzyme and is under control of the molecular switch, wherein the single stranded RNA diagnostic target is a sequence detected by a molecular diagnostic assay. In some embodiments the nucleotide cassette can be used to obtain an RNA expression product. Also provided are vectors and cells comprising the nucleotide cassette or the RNA expression product thereof. The nucleotide cassette can further be used to obtain a diagnostic control composition comprising a non-pathogenic recombinant bacterium having a modified genetic content comprising the nucleotide cassette and to methods of producing such recombinant bacteria.

A fractional concentration of fetal relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments of a particular size or range of sizes. DNA fragments may be sequenced to obtain sequence reads, and the sequence reads may be aligned to a reference genome to determine sizes of the DNA fragments. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a parameter providing a statistical measure of a size profile and the fractional concentration of the fetal DNA. For a given sample, a value of the parameter can be determined from DNA fragments of a particular size or range of sizes in a sample. A comparison of the value to the calibration data points can provide the estimate of the fractional concentration of the fetal DNA.

A fractional concentration of fetal relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments of a particular size or range of sizes. DNA fragments may be sequenced to obtain sequence reads, and the sequence reads may be aligned to a reference genome to determine sizes of the DNA fragments. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a parameter providing a statistical measure of a size profile and the fractional concentration of the fetal DNA. For a given sample, a value of the parameter can be determined from DNA fragments of a particular size or range of sizes in a sample. A comparison of the value to the calibration data points can provide the estimate of the fractional concentration of the fetal DNA.

Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.