Text S1 Adaptive contact networks change effective disease infectiousness and dynamics. 1  The role of infections in the pathogenesis and course of multiple sclerosis Interplay between susceptibility genes and environmental factors is considered important player in the genesis of multiple sclerosis (MS). Among environmental factors, a role for an infectious pathogen has long been considered central to the disease process. This opinion has support both from epidemiological data and the findings of immunological abnormalities in spinal fluid that reflect an immune response to an as yet undetermined antigen, possibly a pathogen, in the cerebrospinal fluid. Our review will outline the current understanding of the role of infection in the causation and progression of MS. We will review the data that point to an infectious cause of MS and consider the specific agents Chlamydophila (Chlamydia) pneumoniae, Human Herpes Virus 6, and Epstein-Barr Virus, that are implicated in either the development or progression of MS.  Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering Ca(2+) plays a pivotal role in the physiology and biochemistry of prokaryotic and mammalian organisms. Viruses also utilize the universal Ca(2+) signal to create a specific cellular environment to achieve coexistence with the host, and to propagate. In this paper we first describe our development of a grafting approach to understand site-specific Ca(2+) binding properties of EF-hand proteins with a helix-loop-helix Ca(2+) binding motif, then summarize our prediction and identification of EF-hand Ca(2+) binding sites on a genome-wide scale in bacteria and virus, and next report the application of the grafting approach to probe the metal binding capability of predicted EF-hand motifs within the streptococcal hemoprotein receptor (Shr) of Streptococcus pyrogenes and the nonstructural protein 1 (nsP1) of Sindbis virus. When methods such as the grafting approach are developed in conjunction with prediction algorithms we are better able to probe continuous Ca(2+)-binding sites that have been previously underrepresented due to the limitation of conventional methodology. Ca 2+ , a signal for "life and death", is involved in almost every aspect of cellular processes. Due to its abundant bioavailability, Ca 2+ was selected through evolution to perform multiple biochemical roles, acting as a second messenger inside mammalian cells to regulate a myriad of important cellular processes from triggering life during fertilization to facilitating apoptosis [1, 2] . As best exemplified by fast responses controlled by highly localized Ca 2+ spikes and slow responses regulated by repetitive global Ca 2+ transient oscillation or intracellular Ca 2+ waves, Ca 2+ signals exhibit diversified spatio-temporal patterns to meet varying demand of cellular processes [3] (Figure 1 ). Errors in any step of the calcium signal pathway can be critical, resulting in uncontrolled cell death or abnormal gene expression [4, 5] .