Deep learning vs conventional learning algorithms for clinical prediction in Crohn's disease: A proof-of-concept study

Table 1 Baseline characteristics of study cohort (n = 146)

Characteristic	n (%)
Age, years, median (IQR)	36 (25-50)
Sex
Female	76 (52)
Male	70 (48)
Smoker (active)	33 (23)
CD behavior
B1: Non-stricturing, non-penetrating	75 (51)
B2: Stricturing	56 (38)
B3: Penetrating/fistulizing	15 (10)
CD location
L1: Ileal	41 (28)
L2: Colonic	43 (29)
L3: Ileocolonic	62 (42)
L4: Isolated UGI	0 (0)
Perianal involvement	20 (21)
Initial anti-TNF commenced
Infliximab	84 (58)
Adalimumab	62 (42)
Baseline thiopurine	99 (68)
Baseline methotrexate	27 (18)
Baseline corticosteroids	64 (44)
Baseline aminosalicylates	48 (33)
Prior anti-TNF	22 (15)
Prior intestinal surgery	41 (28)
Disease duration, yr, median (IQR)	5 (1-12)
Baseline investigations
CRP, mg/L, median (IQR)	3 (2-8)
Albumin, g/L, median (IQR)	37 (36-41)

IQR: Inter-quartile range; CD: Crohn's disease; CRP: C-reactive protein; TNF: Tumor necrosis factor; UGI: Upper gastrointestinal.

Table 2 Estimated odds ratios with 95% confidence intervals on univariable and multivariable logistic regression analysis

Predictor	Univariable		Multivariable
	OR (95%CI)	P value	Adj. OR (95%CI)	P value
Age, per year	0.98 (0.96-1.00)	0.10	-	-
Male (vs female)	1.42 (0.72-2.82)	0.31	-	-
CD behavior
B1	1.0		Not included
B2	0.45 (0.22-0.94)	0.034	Not included
B3	0.42 (0.13-1.29)	0.13	Not included
CD location
L1: ileal	1.0		Not included
L2: colonic	1.33 (0.54-3.31)	0.54	Not included
L3: ileocolonic	0.91 (0.40-2.06)	0.83	Not included
Ileal location (L1)	0.94 (0.45-2.00)	0.88	Not included
Complex disease (B2/B3)	0.44 (0.22-0.89)	0.021	0.36 (0.16-0.80)	0.012
Active smoker	0.76 (0.40-1.47)	0.42	-	-
Perianal involvement	1.14 (0.49-2.65)	0.77	Not included
Anti-TNF type: infliximab (vs adalimumab)	1.12 (0.56-2.22)	0.75	Not included
Baseline immunomodulator	1.24 (0.47-3.27)	0.66	Not included
Baseline corticosteroids	1.10 (0.56-2.18)	0.78	Not included
Baseline aminosalicylates	1.16 (0.56-2.40)	0.69	Not included
Prior anti-TNF	0.96 (0.37-2.47)	0.94	Not included
Prior intestinal surgery	0.71 (0.34-1.48)	0.36	-	-
Disease duration, per loge year	0.83 (0.65-1.06)	0.14	-	-
Albumin, per g/L	1.12 (1.03-1.22)	0.006	1.08 (0.98-1.20)	0.12
Hemoglobin, per g/L	1.01 (0.99-1.04)	0.32	-	-
HCT, per %	0.91 (0.71-1.16)	0.44	-	-
RCC, per 109/L	1.07 (0.84-1.36)	0.60	Not included
MCV, per fL	1.01 (0.96-1.07)	0.64	Not included
MCH, per pg/cell	1.15 (0.99-1.32)	0.06	-	-
MCHC, per mg/L	1.05 (1.02-1.08)	0.002	1.05 (1.02-1.09)	0.004
Platelets, per 100 × 109/L	0.63 (0.43-0.93)	0.020	-	-
Neutrophils, per 109/L	0.91 (0.82-1.00)	0.06	-	-
Lymphocytes, per 109/L	0.66 (0.46-0.93)	0.019	0.65 (0.41-1.02)	0.06
Monocytes, per 109/L	0.23 (0.08-0.63)	0.004	0.34 (0.10-1.16)	0.09
Eosinophils, per 109/L	0.61 (0.08-4.77)	0.64	Not included
Basophils, per 0.01 × 109/L	0.92 (0.80-1.06)	0.24	-	-
Bilirubin, per loge µmol/L	1.38 (0.70-2.72)	0.36	-	-
ALT, per loge IU/L	1.04 (0.60-1.80)	0.90	Not included
ALP, per loge IU/L	0.55 (0.18-1.64)	0.28	-	-
GGT, per loge IU/L	0.71 (0.46-1.09)	0.12	0.69 (0.43-1.11)	0.13

Variables excluded after univariable regression are in grey; variables excluded after stepwise selection are marked with a dash. CI: Confidence interval; OR: Odds ratio; CD: Crohn's disease; TNF: tumor necrosis factor; HCT: Hematocrit; RCC: Red cell count; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase.

Table 3 Comparison of learning algorithms during cross-validation experiments

Algorithm	Dataset1	AUC (%)		P value2
		Mean	SD
Conventional statistics	Baseline clinical + biomarker data	65.9	9.5	-
Feed-forward ANN	Baseline clinical + biomarker data	71.0	8.7	0.25
Feed-forward ANN	Baseline biomarker data only	70.6	8.3	0.33
Recurrent neural network	Baseline and prior biomarker data	75.4	7.8	0.036

¹Clinical data refers to non-biochemical data such as age, sex, disease characteristics and concurrent treatments. Biomarker data refers to complete blood count, liver function tests and albumin.

²P value for comparison against conventional statistical algorithm, using the variance-corrected repeated k-fold t test. AUC: Area under the receiver operator characteristic curve; ANN: Artificial neural network.