2 Autism Research and Treatment Table 1: Potential hypotheses for the relationship between autism and calcineurin. Autism literature Fatemi [28] reported a reduction of Bcl-2 (a regulatory protein for control of programmed brain cell death) levels in the cerebellum of patients with autism. Roesler et al. [47] reported on a translocation in the GRPR gene, the mammalian bombesin-like gastrin-releasing peptide, being associated with autism. Huber et al. [14] showed evidence of an important functional role of fragile X protein, an identiﬁed cause of autism, in regulating activity-dependent synaptic plasticity in the brain. Belmonte et al. [45] reviewed neuropathological studies of the cerebral cortex in autism indicating abnormal synaptic and columnar structure and neuronal migration defects. Vorstman et al. [51] stated that autism spectrum disorders and subthreshold autistic symptoms are common in children with 22q11.2 deletion syndrome. Mouridsen et al. [53] observed two autoimmune conditions associated with infantile autism: ulcerative colitis in mothers and type 1 diabetes in fathers. Rom a´n [55] proposed that morphological brain changes in autism may be produced by maternal hypothyroxinemia resulting in low triiodothyronine in the foetal brain during pregnancy. Omura [57] published the results of measurements of asbestos accumulation where relatively high levels of asbestos were found in autism. Thornton [59] argued that artiﬁcially generated electromagnetic radiation may play an important role in the mirror neuron dysfunction associated with autism. Barnard et al. [61] revealed that adults with autism showed impaired performance on the tests of working memory. Calcineurin literature Erin et al. [30] observed that calcineurin occurred as a complex with Bcl-2 in various regions of rat and mouse brains. Corral et al. [48] showed that bombesin promotes the activation of the nuclear factor of activated T cells (NFAT) through a Ca(2+)/calcineurin-linked pathway. Winder and Sweatt [49] described the critical role of protein phosphatase 1, protein phosphatase 2A, and calcineurin in the activity-dependent alterations of synaptic plasticity. Chen et al. [50] reported about the decrease in protein ubiquitina- tion in synaptosomes and in nonneuronal cells that may play a role in the regulation of synaptic function by a calcineurin antagonist FK506. Sivagnanasundaram et al. [52] examined the diﬀerential expression of gene mapping to human chromosome 22q11.2 in 22q11.2 dele- tion syndrome and found the decreased expression of calmodulin 1 encoding a calcium-dependent protein involved in the calmodulin- calcineurin regulated pathway, which is implicated in learning and memory. Winter and Schatz [54] listed immunosuppression by calcineurin inhibitors as one of the promising strategies for intervention in autoimmune type 1 diabetes mellitus. Sinha et al. [56] found that calcineurin was compromised in young progeny when they investigated the maternal hypothyroxinemia eﬀect during pregnancy on the brains of young progeny. Li et al. [58] investigated the role of reactive oxygen species, by asbestos, in activation of nuclear factor of activated T cells (NFAT). They found that pretreatment of cells with cyclosporin A, a pharmacological inhibitor of calcineurin, blocked asbestos-induced NFAT activation. Manikonda et al. [60] indicated that exposure to extremely low-frequency electromagnetic ﬁelds caused increased activity of calcineurin in the hippocampal region of rats. Runyan et al. [62] illustrated how the inhibition of calcium acti- vated phosphatase calcineurin causes impaired working memory. of symptoms that may be selected as targets for the therapy, and varying degrees of associated symptoms. Besides, ASD has to date been studied in several subﬁelds and at several diﬀerent levels, all using diﬀerent procedures for examina- tion: behavioural psychology, genetics, biochemistry, brain anatomy, physiology, and so forth. The question of how to connect partial results of individual sciences into a complete picture still remains very challenging. One method to manage increasing amounts of specialised knowledge and to support the process of its integration into a bigger and more coherent picture has been presented from knowledge technologies, and more speciﬁcally, from literature mining. This has become possible with the availability of huge online databases, such as PubMed, which covers over 20 million citations. A powerful idea for investigating yet to be explored relationships between biomedical concepts was proposed by Swanson [7]. If there is a relationship between A and B reported in the literature on A, and a relationship between B and C in literature on C, then the concept B, might reveal interesting connections across previously disjoint contexts A and C. Swanson found many relationships, unknown at the time, for example, connecting Raynaud’s syndrome with ﬁsh oil, and migraine headaches with magnesium deﬁciency [7]. The task of ﬁnding the intermediate concepts of B, when A and C are both already known, was deﬁned as closed discovery [8, 9], as opposed to open discovery, where a search proceeds from C towards an unknown A. The latter is a crucial part of the scientiﬁc discovery process when generating new hypotheses. Therefore, our aim was to upgrade the hypothesis generation approach through a more systematic method in the open discovery stage. The basic idea was to use rare terms from the literature on the investigated phenomenon C as a guide toward new discoveries. This idea was ﬁrst presented in Petricˇ et al. [10], as the RaJoLink method. This method has already been tested in the domain of autism [11, 12]. The main novelty regarding Swanson’s method is the choice of candidates for A, which is based on rare terms identiﬁed in the literature on C. If the literature