Analytical choices and mission context shape rodent spaceflight transcriptomic inference

Analytical choices and mission context shape rodent spaceflight transcriptomic inference. Download PDF Abstract Public spaceflight transcriptomes are increasingly reused to identify shared biological responses, but mission context and analytical choices may limit transportability. We evaluated 38 predefined clock- and bile-acid-associated transcripts across eight liver flight-versus-ground contrasts from five biologically independent missions, using Rodent Research-6 (RR-6) only as a reference.

We also audited RR-6 liver and colon inference across alternative count matrices, filtering targets and feature spaces, and tested liver–colon effects directly. Among 37 meta-evaluable targets, one met false-discovery rate < 0.05 and four < 0.10 under normal-theory random-effects inference; none did under modified Hartung–Knapp inference or with |log2 fold change|≥ 1 required. External (non-RR-6) Cyp7a1 effects were heterogeneous (pooled log2 fold change, 0.20; 95% confidence interval, − 0.72 to 1.11; I 2 = 83.4%) and contrasted with RR-6 liver (− 1.54).

Abcg5 was more consistent externally (− 0.20; 95% confidence interval, − 0.33 to − 0.08; I 2 = 0%), but did not retain multiplicity-adjusted support under modified Hartung–Knapp inference or with four added cohorts. In RR-6, broad discovery totals were stable across colon matrices, whereas filtering and feature-space choices altered gene testability and apparent biological totals. Direct tissue testing did not support a Cyp7a1 liver–colon difference.

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