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Novel data can shift learners’ conceptions about science topics. Prior research suggests that such science learning can be supported by bolstering targeted mathematical reasoning skills. This design-based research project aimed to identify specific mathematical skills that might support the interpretation of novel scientific data while concurrently developing an online science learning app. In three design iterations, we conducted 22 think-aloud interviews with undergraduate and graduate students as they estimated climate change data before being shown the scientifically accepted value. Productive strategies included: higher tolerance for error, mental computation (rounding and scaling benchmark values), and integration of prior educational and personal experiences. Results implicate principles for math-science integration and showcase a learning intervention that embodies those principles.