Determining Coronary Artery Disease Risk
AssigneeCardiodx, Inc.
InventorsSteven Rosenberg, Michael R. Elashoff, Philip Beineke, James A. Wingrove, Whittemore G. Tingley, Susan E. Daniels
Life of this patent
Estimating the term…
Abstract
Markers and methods useful for assessing coronary artery disease in a subject are provided, along with kits for measuring their expression. Also provided are predictive models, based on the markers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples.
Claims24
A computer-implemented method for scoring a sample obtained from a subject, comprising:
- obtaining a dataset obtained from the sample, wherein the dataset comprises data representing age and gender and data representing a quantitative expression level value for each of the markers:
- S100A12, CLEC4E, S100A8, CASP5, IL18RAP, TNFAIP6, AQP9, NCF4, CD3D, TMC8, CD79B, SPIB, HNRPF, TFCP2, RPL28, AF161365, AF289562, SLAMF7, KLRC4, IL8RB, TNFRSF10C, KCNE3, and TLR4;
- and
- applying an interpretation function to the dataset to mathematically combine, by a computer processor, the data representing the quantitative expression level value for each marker to predict the presence or absence of coronary artery disease (CAD) in the subject, wherein the interpretation function is:
- Score=INTERCEPT−0.755*(Nup−Ndown)−0.406*(NKup−Tcell)−0.308*SEX*(SCA1−Norms)−0.137*(Bcell−Tcell)−0.548*(1−SEX)*(SCA1−Neut)−0.482*SEX*(TSPAN)−0.246*(AF2−Norm2), wherein Norm1=RPL28, wherein Norm2=(0.5*HNRPF+0.5*TFCP2), wherein NKup=(0.5*SLAMF7+0.5*KLRC4), wherein Tcell=(0.5*CD3D+0.5*TMC8), wherein Bcell=(⅔*CD79B+⅓*SPIB), wherein Neut=(0.5*AQP9+0.5*NCF4), wherein Nup=(⅓*CASP5+⅓*IL18RAP+⅓*TNFAIP6), wherein Ndown=(0.25*IL8RB+0.25*TNFRSF10C+0.25*TLR4+0.25*KCNE3), wherein SCA1=(⅓*S100A12+⅓*CLEC4E+⅓*S100A8), wherein AF2=AF289562, wherein TSPAN=1 if (AF161365-Norm2>6.27 or AF161365=NoCall), 0 otherwise, wherein SEX=1 for Males, 0 for Females, and wherein for males INTERCEPT=2.672+0.0449*Age or for females INTERCEPT=1.821+0.123*(Age-60), if negative set to 0, thereby scoring the sample obtained from the subject.
A system for scoring a sample obtained from a subject, the system comprising:
- a storage memory for storing a dataset obtained from a sample obtained from the subject, wherein the dataset comprises data representing age and gender and data representing a quantitative expression level value for each of the markers:
- S100A12, CLEC4E, S100A8, CASP5, IL18RAP, TNFAIP6, AQP9, NCF4, CD3D, TMC8, CD79B, SPIB, HNRPF, TFCP2, RPL28, AF161365, AF289562, SLAMF7, KLRC4, IL8RB, TNFRSF10C, KCNE3, and TLR4;
- and
- a processor communicatively coupled to the storage memory for applying an interpretation function to the dataset to mathematically combine the data representing the quantitative expression level value for each marker to predict the presence or absence of coronary artery disease (CAD) in the subject, wherein the interpretation function is:
- Score=INTERCEPT−0.755*(Nup−Ndown)−0.406*(NKup−Tcell)−0.308*SEX*(SCA1−Norm1)−0.137*(Bcell−Tcell)−0.548*(1−SEX)*(SCA1−Neut)−0.482*SEX*(TSPAN)−0.246*(AF2−Norm2), wherein Norm1=RPL28, wherein Norm2=(0.5*HNRPF+0.5*TFCP2), wherein NKup=(0.5*SLAMF7+0.5*KLRC4), wherein Tcell=(0.5*CD3D+0.5*TMC8), wherein Bcell=(⅔*CD79B+⅓*SPIB), wherein Neut=(0.5*AQP9+0.5*NCF4), wherein Nup=(⅓*CASP5+⅓*IL18RAP+⅓*TNFAIP6), wherien Ndown=(0.25*IL8RB+0.25*TNFRSF10C+0.25*TLR4+0.25*KCNE3), wherein SCA1=(⅓*S100A12+⅓*CLEC4E+⅓*S100A8), wherein AF2=AF289562, wherein TSPAN=1 if (AF161365-Norm2>6.27 or AF161365=NoCall), 0 otherwise, wherein SEX=1 for Males, 0 for Females, and wherein for males INTERCEPT=2.672+0.0449*Age or for females INTERCEPT=1.821+0.123*(Age-60), if negative set to 0, thereby scoring the sample obtained from the subject.
A computer-readable storage medium storing computer-executable program code for scoring a sample obtained from a subject, the medium comprising:
- a dataset obtained from the sample, wherein the dataset comprises data representing age and gender and data representing a quantitative expression level value for each of the markers:
- S100A12, CLEC4E, S100A8, CASP5, IL18RAP, TNFAIP6, AQP9, NCF4, CD3D, TMC8, CD79B, SPIB, HNRPF, TFCP2, RPL28, AF161365, AF289562, SLAMF7, KLRC4, IL8RB, TNFRSF10C, KCNE3, and TLR4;
- and
- computer-executable program code for applying an interpretation function to the dataset to mathematically combine the data representing the quantitative expression level value for each marker to predict the presence or absence of coronary artery disease (CAD) in the subject, wherein the interpretation function is:
- Score=INTERCEPT−0.755*(Nup−Ndown)−0.406*(NKup−Tcell)−0.308*SEX*(SCA1−Norm1)−0.137*(Bcell−Teen)−0.548*(1−SEX)*(SCA1−Neut)−0.482*SEX*(TSPAN)−0.246*(AF2−Norm2), wherein Norm1=RPL28, wherein Norm2=(0.5*HNRPF+0.5*TFCP2), wherein NKup=(0.5*SLAMF7+0.5*KLRC4), wherein Tcell=(0.5*CD3D+0.5*TMC8), wherein Bcell=(⅔*CD79B+⅓*SPIB), wherein Neut=(0.5*AQP9+0.5*NCF4), wherein Nup=(⅓*CASP5+⅓*IL18RAP+⅓*TNFAIP6), wherein Ndown=(0.25*IL8RB+0.25*TNFRSF10C+0.25*TLR4+0.25*KCNE3), wherein SCA1=(⅓*S100A12+⅓*CLEC4E+⅓*S100A8), wherein AF2=AF289562, wherein TSPAN=1 if (AF161365-Norm2>6.27 or AF161365=NoCall), 0 otherwise, wherein SEX=1 for Males, 0 for Females, and wherein for males INTERCEPT=2.672+0.0449*Age or for females INTERCEPT=1.821+0.123*(Age-60), if negative set to 0, thereby scoring the sample obtained from the subject.
Dependencies are inferred from the claim text.