Trang Lê
University of Pennsylvania
BIOSTEC, Bioinformatics, Valletta, Malta
2020-02-25
Individuals with high genetic risk scores for a disease are more susceptible to that disease
and may benefit from prioritized interventions.
\[PRS(i)=\sum_{j=1}^{k} \beta_j \times SNP_{ij}\]
a
effect size of \(SNP_j\) in discovery sample from OLS or logistic reg.
a
subject
number of minor alleles at \(SNP_j\)
for subject \(i\)
a
Probabilistic susceptibility
→ identify groups of individuals who need prioritized interventions and screenings
→ life planning
\[PRS(i)=\sum_{j=1}^{k} \beta_j \times SNP_{ij}\]
Polygenic Risk Scores
Multilocus Risk Scores
MRS method utilizes
model-based multifactor dimensionality reduction (MB-MDR).
HLO matrix
High = 1
Low = -1
O = 0
\(\gamma\)
\[MRS_d(i) = \sum_{j = 1}^{k_d} \gamma_j \times \textrm{HLO}_j(X_{ij})\]
\[PRS(i)=\sum_{j=1}^{k} \beta_j \times SNP_{ij}\]
a
interaction dimension
a
SNP combination
a
\(j^{th}\) HLO matrix
a
MB-MDR test statistic
a
subject
\[MRS_d(i) = \sum_{j = 1}^{k_d} \gamma_j \times \textrm{HLO}_j(X_{ij})\]
\[MRS_2(Alice) = 0.8\times 1 + \cdots\]
Bob has the combination (aa, aa) for these two SNPs.
\(\gamma = 0.8\)
\[MRS_2(Bob) = 0.8\times (-1) + \cdots\]
Suppose Alice has the combination (AA, Aa) and
450 datasets: 1000 individuals and 10 SNPs
For an individual, each genotype was randomly assigned with:
Evolutionary-based method: Heuristic Identification of Biological Architectures for simulating Complex Hierarchical Interactions (HIBACHI)
MRS produces improved auROC in 335 of 450 simulated datasets.
~50% auROC increase at the second peak
\(MRS = MRS_1 + MRS_2\) increasingly outperforms standard PRS
as dataset contains more main and interaction effects.
\[ME = \sum_{j} I(SNP_j; Y) = \sum_{j} \left(H(Y) - H(Y|SNP_j)\right).\]
\[SE = \sum_{j} IG(X_j; Y) = \sum_{j} \left(I(SNP_{j_1}, SNP_{j_2}; Y) - I(SNP_{j_1}; Y) - I(SNP_{j_2}; Y)\right)\]
Hoyt Gong
Elisabetta Manduchi
Patryk Orzechowski
Jason H. Moore
funded by the
National Institutes of Health
BIOSTEC organizers
Want to run the Victoria Lines?
Meet me at Excelsior Level 1, 5:45 AM tomorrow (Wednesday).
My (optimistic) estimate: ~ 3 hours, 18 km, 600 m vertical gain