Journal: Cell Reports Medicine

Article Title: GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

doi: 10.1016/j.xcrm.2023.101344

Figure Lengend Snippet: GIInger predicts HRD status using spatially organized coverage profiles from lpWGS data (A) Study overview. (B) Example of GIInger input. Heatmap of the smoothed normalized coverage across ∼3 Mbp bins (columns) for all autosomes (rows) aligned with respect to their centromere (vertical dashed line). Bins are colored (blue-white-red scale) based on their normalized coverage relative to the mean coverage of the sample (set to 1, white). Color scale is depicted on the bottom. NaN (“not a number”) refers to non-existing relative chromosome locations. (C) GIInger architecture schematic. Input features are extracted through a series of convolution and pooling operations. The vector containing the 48 extracted features is provided to a set of fully connected layers trained to output the GIInger score, which predicts the sample’s genomic instability (GI) status based on the score threshold.

Article Snippet: • GIInger is available as part of the SOPHiA GENETICS SOPHiA DDM platform.

Techniques: Plasmid Preparation

Journal: Cell Reports Medicine

Article Title: GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

doi: 10.1016/j.xcrm.2023.101344

Figure Lengend Snippet: GIInger yields comparable results in predicting HRD status to tools that rely on high-coverage datasets (A) 101 breast cancer samples (x axis) and GIInger scores (y axis), ordered by GIInger score and colored according to their HRD status according to HRDetect as positive (blue) and negative (gray) and patterned according to their BRCA status as mutated (cross-hatching) and wild type (no hatching). (B) ROC curves for breast cancer HRD classification obtained using GIInger (red), LST (orange), GIS (green), LOH score (pink), and BRCA status (blue) using HRD status reported by HRDetect as reference. AUC values for each method are given within the insets.

Article Snippet: • GIInger is available as part of the SOPHiA GENETICS SOPHiA DDM platform.

Techniques:

Journal: Cell Reports Medicine

Article Title: GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

doi: 10.1016/j.xcrm.2023.101344

Figure Lengend Snippet: GIInger analytical performance analysis in clinical samples (A) Representation of the multicenter study design. (B) Concordance of GI status between GIInger and the reference method (n = 296 samples). For details on rejection criteria, see . (C) GIInger scores (y axis) relative to the corresponding reference method GI score (x axis). Each point corresponds to a cancer patient sample (n = 125) and is labeled according to the GI status concordance between the two methods. Dashed lines indicate respective classification thresholds of GIInger and the reference method. Solid line indicates linear regression best fit; R 2 = 0.85.

Article Snippet: • GIInger is available as part of the SOPHiA GENETICS SOPHiA DDM platform.

Techniques: Labeling

Journal: Cell Reports Medicine

Article Title: GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

doi: 10.1016/j.xcrm.2023.101344

Figure Lengend Snippet: GIInger clinical relevance analysis (A) Properties of samples included in the full PAOLA-1 cohort and the subset included in the present study. PFS curves stratified by treatment arms (orange: olaparib plus bevacizumab; gray: placebo plus bevacizumab) in the PAOLA-1 subcohort (n = 195) according to (B) GI-positive status assigned by GIInger (HR: 0.49, 95% CI: 0.28–0.85; p = 0.01) and (C) GI-negative status assigned by GIInger (HR: 0.82, 95% CI: 0.52–1.31; p = 0.41); y axis: probability of patients being free from disease progression and death; x axis: months since randomization; dashed lines indicate median survival times; and tables of absolute number of individuals at risk are given below each plot.

Article Snippet: • GIInger is available as part of the SOPHiA GENETICS SOPHiA DDM platform.

Techniques:

Journal: Cell Reports Medicine

Article Title: GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

doi: 10.1016/j.xcrm.2023.101344

Figure Lengend Snippet: GIInger is a flexible and robust patient stratification method (A) Workflow schematics illustrating flexible use of GIInger in combined workflow with existing targeted sequencing approaches. Pre-capture library aliquots can be sequenced at ∼1× depth and inform sample HRD status together with data on BRCA status. (B) Qualitative workflow cost and complexity comparison of different methodologies for determining HRD-related biomarkers genome instability and BRCA status. CGP, comprehensive genomic profiling. Inferences are based on relative differences detailed in Table S3 . (C) Concordance of GIInger scores between lpWGS-only (y axis) and combined (i.e., targeted sequencing with HRDv1 panel + lpWGS) workflow (x axis). Each point corresponds to a PAOLA-1 cancer patient sample (n = 124) and is labeled according to the GI status concordance between the two workflows. Dashed lines represent GIInger classification threshold, and solid line indicates linear regression best fit; R 2 = 0.99; overall concordance: 97.58% (95.31%, 99.55%).

Article Snippet: • GIInger is available as part of the SOPHiA GENETICS SOPHiA DDM platform.

Techniques: Sequencing, Comparison, Labeling