BACKGROUND: Fungal-based composites have emerged as renewable, high-performance biomaterials that are produced on lignocellulosic residual streams from forestry and agriculture. Production at an industrial scale promises to revolutionize the world humans inhabit by generating sustainable, low emission, non-toxic and biodegradable construction, packaging, textile, and other materials. The polypore Fomes fomentarius is one of the basidiomycete species used for biomaterial production, yet nothing is known about the transcriptional basis of substrate decomposition, nutrient uptake, or fungal growth during composite formation. Co-expression network analysis based on RNA-Seq profiling has enabled remarkable insights into a range of fungi, and we thus aimed to develop such resources for F. fomentarius. RESULTS: We analysed gene expression from a wide range of laboratory cultures (n = 9) or biomaterial formation (n = 18) to determine the transcriptional landscape of F. fomentarius during substrate decomposition and to identify genes important for (i) the enzymatic degradation of lignocellulose and other plant-based substrates, (ii) the uptake of their carbon monomers, and (iii) genes guiding mycelium formation through hyphal growth and cell wall biosynthesis. Simple scripts for co-expression network construction were generated and tested, and harnessed to identify a fungal-specific transcription factor named CacA strongly co-expressed with multiple chitin and glucan biosynthetic genes or Rho GTPase encoding genes, suggesting this protein is a high-priority target for engineering adhesion and branching during composite growth. We then updated carbohydrate activated enzymes (CAZymes) encoding gene annotation, used phylogenetics to assign putative uptake systems, and applied network analysis to predict repressing/activating transcription factors for lignocellulose degradation. Finally, we identified entirely new types of co-expressed contiguous clusters not previously described in fungi, including genes predicted to encode CAZymes, hydrophobins, kinases, lipases, F-box domains, chitin synthases, amongst others. CONCLUSION: The systems biology data generated in this study will enable us to understand the genetic basis of F. fomentarius biomaterial formation in unprecedented detail. We provided proof-of-principle for accurate network-derived predictions of gene function in F. fomentarius and generated the necessary data and scripts for analysis by any end user. Entirely new classes of contiguous co-expressed gene clusters were discovered, and multiple transcription factor encoding genes which are high-priority targets for genetic engineering were identified.