Koninklijke Philips Corporation N.v.

Innosign B.v.

Hendrik Jan Van Ooijen

Wilhelmus Franciscus Johannes Verhaegh

Anja Van De Stolpe

Bart Jacob Bakker

Marcia Alves De Inda

Rene Van Den Ham

Dianne Arnoldina Margaretha Wilhelmina Van Strijp

Anne Godefrida Catharina Van Brussel

Robert Van Gog

Ralf Hoffmann

Paul Arnold Van De Wiel

Janneke Wrobel

Ralf Dieter Hoffmann

René Van Den Ham

Kalyana Chakravarthi Dulla

Jenneke Wrobel

Wilhelmus Franciscus Verhaegh

Márcia Alves De Inda

Anja Vande Stolpe

The invention relates to a method for predicting a value of a parameter of a system (). The value of the parameter of the system () is predicted by incrementally optimizing a pharmacokinetic and pharmacodynamic model based on values of parameters of the system () received over time. This allows for predicting values of the parameters of the system () with improved accuracy. In one embodiment the system () comprises a coagulation system () comprising an anticoagulant. The predicted value of the parameter of the system () can be a point in time at which the coagulation system () reaches hemostatic balance after a periodic supply of anticoagulant to the coagulation system () is discontinued.

Incrementally optimized pharmacokinetic and pharmacodynamic model

A bioinformatics method for determining a risk score that indicates a risk that a subject will experience a negative clinical event within a certain period of time. The risk score is based on a combination of activities of two or more cellular signaling pathways in a subject, such as a human, wherein the specific cellular signaling pathways are the PI3K pathway and one or more of a Wnt pathway, an ER pathway, and an HH pathway. The invention also includes an apparatus with a digital processor configured to perform such a method, to a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and to a computer program comprising program code means for causing a digital processing device to perform such a method. The invention achieves advanced prognosis of negative clinical events, for example, disease progression, recurrence, development of metastasis, or even death.

Bioinformatics process for identifying at risk subject populations

A bioinformatics method for determining a risk score that indicates a risk that a subject, in particular a human, will experience a negative clinical event within a certain period of time. The risk score is based on a unique combination of activities of two or more cellular signaling pathways in a subject, wherein the selected cellular signaling pathways are the TGF-&#x3b2; pathway and one or more of a PI3K pathway, a Wnt pathway, an ER pathway, and an HH pathway. The invention includes an apparatus with a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. The bioinformatics invention allows for more accurate prognosis of specific negative clinical events in a patient with, for example, a tumor or cancer, such as disease progression, recurrence, development of metastasis, or even death.

Superior bioinformatics process for identifying at risk subject populations

The present invention relates to clinical decision support systems. In detail, the present invention relates to a method for determining the initial fibrinogen concentration in a biological sample, to the use of fibrinogen added to a biological sample in at least one predetermined concentration, to a device for determining the initial fibrinogen concentration in a biological sample, to a computer program comprising program code means for causing a computer to carry out at least several steps of the method according to the invention, to a computer readable non-transitory storage medium containing instructions for carrying out at least some steps of the method according to the invention, and to a kit for determining the initial fibrinogen concentration in a biological sample.

Method for determining the fibrinogen concentration in a biological sample

A bioinformatics process which provides an improved means to detect NFkB cellular signaling pathway in a subject, such as a human, based on the expression levels of at least six unique target genes of the NFkB cellular signaling pathway measured in a sample. The invention includes an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. Kits are also provided for measuring expression levels of unique sets of NFkB cellular signaling pathway target genes.

Determination of NFkB pathway activity using unique combination of target genes

The present application mainly relates to specific methods for inferring activity of one or more cellular signaling pathway(s) in tissue of a medical subject based at least on the expression level(s) of one or more target gene(s) of the cellular signaling pathway(s) measured in an extracted sample of the tissue of the medical subject, an apparatus comprising a digital compressor configured to perform such methods and a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such methods.

Assessment of cellular signaling pathway activity using probabilistic modeling of target gene expression

The present application mainly relates to specific methods for inferring activity of a cellular signaling pathway in tissue and/or cells of a medical subject based at least on expression levels of one or more target gene(s) of the cellular signaling pathway measured in an extracted sample of the tissue and/or cells of the medical subject, an apparatus comprising a digital compressor configured to perform such methods and a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such methods.

Assessment of cellular signaling pathway activity using linear combination(s) of target gene expressions

A method for determining a risk score that indicates a risk that a clinical event will occur within a certain period of time. The risk score is based at least in part on a combination of inferred activities of two or more cellular signaling pathways in a tissue and/or cells and/or a body fluid of a subject. The cellular signaling pathways comprise a Wnt pathway, an ER pathway, an HH pathway, and/or an AR pathway. The risk score is defined such that the indicated risk that the clinical event will occur within the certain period of time decreases with an increasing PER and increases with an increasing max(PWnt, PHH), wherein PER, PWnt, and PHH denote the inferred activity of the ER pathway, the Wnt pathway, and the HH pathway, respectively.

Medical prognosis and prediction of treatment response using multiple cellular signalling pathway activities

The present invention relates to device () for determining a fibrinogen level () in a sample () comprising, a first input for obtaining an attenuance signal () over time indicative of a fibrin polymerization of said sample (), a second input for obtaining a reactant concentration signal () over time indicative of a reactant concentration in said sample (), wherein the reactant is any substance leading to the cleavage of fibrinogen to fibrin, a simulation unit () running a model () using the reactant concentration signal () as an input to provide a simulated attenuance signal () over time, and an evaluation unit () configured to infer the fibrinogen level () of said sample () by comparing the attenuance signal () over time with the simulated attenuance signal () over time.

Device, system and method for determining a fibrinogen level in a blood sample

A bioinformatics process which provides an improved means to detect TGF-&#x3b2; cellular signaling pathway in a subject, such as a human, based on the expression levels of one or more unique target gene(s) of the TGF-&#x3b2; cellular signaling pathway measured in a sample. The invention includes an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. Kits are also provided for measuring expression levels of unique sets of TGF-&#x3b2; cellular signaling pathway target genes.

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Eindhoven, Netherlands

Hendrik Jan Van Ooijen