Perturb-and-Restore: Simulation-driven Structural Augmentation Framework for Imbalance Chromosomal Anomaly Detection
Authors: Yilan Zhang, Hanbiao Chen, Changchun Yang, Yuetan Chu, Siyuan Chen, Jing Wu, Jingdong Hu, Na Li, Junkai Su, Yuxuan Chen, Ao Xu, Xin Gao, Aihua Yin
Organizations: Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia · Center of Excellence on Smart Health (KCSH) and Center of Excellence for Generative AI, KAUST, Thuwal 23955-6900, Saudi Arabia · Guangdong Provincial Maternal and Child Health Hospital, Guangzhou 511442, China · Smiltec, Suzhou 215125, China
Detecting structural chromosomal abnormalities is crucial for accurate diagnosis and management of genetic disorders. However, collecting sufficient structural abnormality data is extremely challenging and costly in clinical practice, and not all abnormal types can be readily collected. As a result, deep learning approaches face significant performance degradation due to the severe imbalance and scarcity of abnormal chromosome data. To address this challenge, we propose a Perturb-and-Restore (P&R), a simulation-driven structural augmentation framework that effectively alleviates data imbalance in chromosome anomaly detection. The P&R framework comprises two key components: (1) Structure Perturbation and Restoration Simulation, which generates synthetic abnormal chromosomes by perturbing chromosomal banding patterns of normal chromosomes followed by a restoration diffusion network that reconstructs continuous chromosome content and edges, thus eliminating reliance on rare abnormal samples; and (2) Energy-guided Adaptive Sampling, an energy score-based online selection strategy that dynamically prioritizes high-quality synthetic samples by referencing the energy distribution of real samples. To evaluate our method, we construct a comprehensive structural anomaly dataset consisting of over 260,000 chromosome images, including 4,242 abnormal samples spanning 24 categories. Experimental results demonstrate that the P&R framework achieves state-of-the-art (SOTA) performance, surpassing existing methods with an average improvement of 8.92% in sensitivity, 8.89% in precision, and 13.79% in F1-score across all categories.
Figures & tables
Figure 1: Thoughts of Perturb-and-Restore (P&R). P&R mitigates the impact of long-tailed chromosomal distributions by simulating diverse structural anomalies from normal chromosomes. Guided by prior knowledge, structural perturbations are introduced to specific regions and refined via diffusion-based restoration. An energy-guided sampling strategy then selects high-quality synthetic anomalies to enhance the training of robust anomaly detectors.
Figure 2: The flowchart of the Structure Perturbation and Restoration Simulation (SPRS) module: (a) Chromosome skeletons are extracted and segmented into rectangular patches. (b) Structural perturbation operations are applied to rearranged chromosomes using prior knowledge.(c) The rearranged chromosomes and their original counterparts are paired to train a diffusion-based restoration model that treats rearrangement as image degradation. (d) The trained restoration model refines these synthetic anomalies by restoring realistic edges and content, generating highly realistic abnormal samples.
Figure 3: Framework of the proposed Perturb-and-Restore (P&R) method. (a) The SPRS module generates synthetic abnormal chromosomes by simulating structural anomalies based on prior abnormality knowledge. (b) The EAS module performs dynamic online sampling of synthetic data during training. By referencing the energy distributions of real normal and abnormal samples, the model selects high-quality synthetic anomalies to enhance detection performance.
Category
Train
Validation (200 Normal)
Test (800 Normal)
Unbalance Ratio
Synthetic Abnormality
1
343:10227
57
170
29.81
7926
2
72:10217
12
33
141.90
8438
3
42:10276
7
20
244.67
8799
4
51:10275
8
25
201.47
9136
5
44:10273
7
22
233.48
9269
6
83:10271
14
40
123.75
8913
Table 1: Summary of the chromosome used in this study. Each category corresponds to one of the 24 chromosome types (1–22, X, and Y). Values in the train column represent the number of abnormal versus normal chromosomes ( Abnormal:Normal ). The validation and test sets each include 200 and 800 normal samples per category. The unbalance ratio quantifies the level of class imbalance ( Normal/Abnormal ), while the synthetic abnormality column lists the number of synthetic abnormal chromosomes
Methods
Acc ↑
Sen ↑
Spe ↑
Pre(ab) ↑
Pre(n) ↑
AUC ↑
F1 ↑
ResNet18
Baseline
95.94 (2.79)
30.13 (31.21)
99.22 (1.76)
65.99 (44.67)
96.37 (2.23)
79.36 (11.79)
33.92 (31.20)
Under-sampling
91.39 (7.17)
50.38 (22.34)
93.39 (7.41)
41.43 (26.68)
97.22 (2.19)
83.99 (9.46)
38.27 (18.94)
Over-sampling
96.11 (3.28)
53.63 (15.98)
98.12 (2.59)
71.17 (19.67)
97.57 (1.75)
91.44 (4.87)
58.75 (13.32)
Focal Loss
95.33 (4.91)
54.52 (16.50)
97.96 (3.81)
70.88 (14.92)
96.01 (7.86)
91.16 (5.06)
59.44 (11.46)
LDAM-DRW
95.85 (4.70)
54.97 (15.64)
97.56 (5.04)
68.63 (13.48)
97.77 (1.38)
91.18 (4.65)
59.59 (11.83)
Table 2: Performance comparison of different methods for chromosomal anomaly detection (mean(std) %). The best results and the second-best results are highlighted in Bold and in underline .
Figure 4: Radar chart of chromosomal anomaly detection on 24 categories (sensitivity, precision of abnormality, and F1 score).
Figure 5: Performance comparisons under different imbalance ratio levels.
SYN
SYN*
EAS
Acc ↑
Sen ↑
Spe ↑
Pre(ab) ↑
Pre(n) ↑
AUC ↑
F1 ↑
p1
p2
ResNet18
95.94 (2.79)
30.13 (31.21)
99.22 (1.76)
65.99 (44.67)
96.37 (2.23)
79.36 (11.79)
33.92 (31.20)
⋆
-
✓
95.91 (3.00)
30.65 (24.13)
95.34 (16.88)
63.75 (28.18)
96.81 (1.57)
84.42 (10.38)
37.77 (24.79)
⋆ 0.328
△
✓
✓
96.42 (3.19)
55.30 (16.25)
98.42 (2.49)
71.90 (12.30)
97.65 (1.97)
90.75 (4.37)
60.88 (12.05)
⋆ 4.24×10−5
△ 3.77×10−6
✓
97.38 (2.64)
69.14 (16.90)
98.58 (2.84)
74.85 (12.76)
98.54 (0.94)
95.94 (3.51)
70.91 (13.62)
⋆ 1.19×10−6
▽
✓
✓
97.23 (2.98)
70.06 (12.04)
98.44 (2.79)
78.24 (11.97)
98.48 (1.07)
95.00 (2.75)
73.03 (9.54)
⋆ 1.51×10−7
▽ 0.226
Table 3: Performance comparison with different components. SYN represents the abnormality simulation data before restoration, while SYN* denotes the synthetic data after restoration. p1 indicates the p-value of the paired t-test relative to the baseline, while p2 represents the p-value relative to the model without EAS.
Methods
Acc ↑
Pre(ab) ↑
Sen ↑
F1 ↑
AUC ↑
CE
95.94 (2.79)
65.99 (44.67)
30.13 (31.21)
33.92 (31.20)
79.36 (11.79)
CE+SYN*
97.38 (2.64) ↑ 1.44
74.85 (12.76) ↑ 8.86
69.14 (16.90) ↑ 39.01
70.91 (13.62) ↑ 36.99
95.94 (3.51) ↑ 16.58
ReAD
96.29 (3.09)
73.86 (15.71)
48.61 (18.75)
56.17 (15.21)
91.21 (4.37)
ReAD+SYN*
96.58 (2.67) ↑ 0.29
76.87 (15.31) ↑ 3.01
53.41 (18.11) ↑ 4.8
60.67 (14.60) ↑ 4.5
91.39 (4.79) ↑ 0.18
Energy_ood
96.04 (3.57)
68.69 (16.71)
54.58 (17.81)
58.94 (14.39)
91.72 (5.54)
Energy_ood+SYN*
97.47 (2.60) ↑ 1.43
73.77 (13.05) ↑ 5.08
71.09 (17.44) ↑ 16.51
71.64 (14.59) ↑ 12.7
95.12 (3.78) ↑ 3.4
Table 4: Performance improvement across different methods with and without SYN*
Acc ↑
Pre(ab) ↑
Sen ↑
F1 ↑
AUC ↑
Coefficient λ
0.1
97.23 (2.98)
78.24 (11.97)
70.06 (12.04)
73.03 (9.54)
95.00 (2.75)
1
97.26 (2.22)
74.67 (10.97)
69.87 (10.53)
71.89 (9.79)
94.09 (3.48)
10
97.61 (2.46)
83.48 (10.48)
65.12 (15.07)
72.30 (12.12)
92.08 (5.77)
Interval k
5
96.74 (4.37)
70.55 (13.28)
73.84 (13.28)
71.54 (10.68)
94.77 (3.56)
Table 5: Anomaly detection performance under varying loss weights ( λ ) and sampling intervals ( k ).
Restoration
KID ↓
Iter
PSNR ↑
SSIM ↑
vs. Normal
vs. Abnormal
0
-
-
0.0412
0
10K
29.94
0.9687
0.0324
0.0460
50K
30.51
0.9678
0.0305
0.0342
100K
31.66
0.9708
0.0159
0.0318
150K
33.68
0.9768
0.0144
0.0325
Table 6: Restoration and detection performance at different iterations of training restoration model. For KID, the value at Iter 0 represents the divergence between real abnormal and normal chromosome images before restoration training.
Acc ↑
Group 1
Group 2
p -value
Per-user Acc
52.29 (5.20)
53.29 (6.76)
0.779
Acc ↑
Real Images
Synthetic Images
p -value
Per-image Acc
62.57 (15.36)
43.00 (14.81)
4.86×10−9
Table 7: Results of user study
Figure 6: Visualization of Energy score distributions for normal, abnormal, and synthetic data. (Top) Evolution of energy distributions for Chr1 over training epochs, showing progressive separation between normal (blue) and abnormal (red and orange) samples. (Bottom) Final energy score distributions across representative chromosomes with varying imbalance ratios (i.r.), demonstrating that the proposed EAS module maintains clear separability between normal and abnormal classes even under extreme imbalance conditions (please zoom in to view finer details).
Software College, Northeastern University Shenyang, China · Tianjin University Tianjin, China · School of Computer Science and Engineering, Northeastern University Shenyang, China +1