Development of a scoring function for comparing simulated and experimental tumor spheroids
Fig 7
Deviation score comparison for in vitro MDA-MB-231 spheroids cultured in four collagen concentrations c (data provided by Kang et al [13]).
a) 2D cross-sections of 3D multiphoton microscopy image stacks depicting one replicate of each collagen concentration [13]. Spheroids were imaged at one, two or three days after embedding in collagen, and were then fixed and imaged (see Section 4.3). b) Deviation score comparison between all spheroid samples. For each day, the deviation scores for three replicates of each collagen concentration are shown on the upper triangle, and the average deviation score for each collagen concentration is shown on the lower triangle. A top-down view of the spheroid point cloud for a representative replicate of each collagen concentration is shown next to each heatmap (see S2 Fig for all replicates). Blue cells are classified as non-gaslike, and red cells are classified as gaslike. Due to matching initial conditions, we observe low deviation scores between spheroids grown for one day. These differences increase at day 2, where we observe an approximately linear increase of the average deviation score from c = 1 mg/ml to c = 4 mg/ml. Finally, at day 3, we observe the lowest deviation between c = 3 mg/ml and c = 4 mg/ml. This underlines the findings by Kang et al., who observed a transition in invasion behavior between 2 mg/ml and 3 mg/ml. c) Deviation score box plots from spheroids grown for one, two and three days respectively. The box plots for each day show the deviation score values between c = 1 mg/ml and each other concentration. These values correspond to those used for the lowest rows in b). We observe that for spheroids grown for one and two days, the deviation score values of c = 1 mg/ml compared with itself are similar to the deviation score values of c = 1 mg/ml compared with the other concentrations. The differences are nonsignificant and therefore not sufficient to clearly distinguish between the concentrations. This changes at day three, where each concentration shows a higher deviation score to c = 1 mg/ml than c = 1 mg/ml compared with itself. Significance was determined using Welch’s t-test.