**1. Introduction**

Genome-wide approaches to identify genes that are differentially expressed under different conditions of interest have become a standard approach to investigating mechanisms involved in biological processes. The analysis pipeline used in such studies generally leads quickly to some form of gene ontology analysis, in order to identify biological functions that are associated with the differentially regulated genes. A complementary approach would be to analyse differentially regulated genes in relation to predicted conformational properties of the proteins they encode but such an approach has not been reported.

Characterisation of differentially regulated genes in relation to predicted or known conformational properties of the proteins they encode would be of interest in the light of recent discoveries showing overall relationships between conformational properties and different types of protein functionality or mechanism of action [1]. For example, the catalytic domains of enzymes are generally ordered globular conformations while transcription factors are characterised by a preponderance of intrinsic disorder leading to ensembles of many alternative conformational forms [2]. It is now clear that about half the proteins in eukaryotes contain at least one extended (>30 amino acid residues) intrinsically disordered region (IDR) and some proteins are completely disordered [3].

Interestingly, IDRs occur more frequently in regulatory proteins and disease-related proteins [4,5]. We recently identified genes that are differentially expressed in mantle cell lymphoma (MCL) cells that adhere to stromal cells with which they are co-cultured compared to non-adherent MCL cells in the same culture [6]. The differentially regulated gene set defined in this in vitro model system showed substantial overlap with genes that are differentially regulated in the lymph node microenvironment of MCL and chronic lymphoblastic leukaemia (CLL) patients. Retention of lymphoma cells in microenvironments is thought to lead to minimal residual disease, in which a subpopulation of cancer cells receives survival signals from normal cells in microenvironments, thus allowing them to survive during treatment and to subsequently cause disease relapse. In vitro, minimal residual disease is mimicked by cell adhesion mediated drug resistance whereby, for example, lymphoma cells residing in close proximity to stromal cells manifest an enhanced level of resistance to cytostatic drugs [7]. Thus, differentially regulated genes in co-cultured adherent lymphoma cells are likely to represent processes important for cell adhesion mediated drug resistance and minimal residual disease.

In our recent study, we identified 1050 genes that were differentially regulated in MCL cells adhered to stromal cells compared to non-adherent MCL cells in the same co-culture. The four main functional themes characterised by the differentially regulated gene set were cell adhesion, anti-apoptosis and B-cell signalling/immune-modulation, associated with up-regulated genes in adherent cells, as well as early mitotic processes, associated with down-regulated genes [6]. Here we test whether the differentially regulated gene set or its subsets encode proteins that differ in IDR properties compared to non-regulated genes.
