These application notes show the power of the Literature Lab™ and Literature Lab™ PLUS tools.
Schizophrenia (SZ) is now known to be a neurodevelopmental disease, however, research to date has been based largely on end point post mortem brain tissue and animal models. Stem cell models have very recently been developed, offering promise as platforms for greater disease understanding and diagnostic and therapeutic discovery.
We enlisted Literature Lab™ PLUS to explore published microarray data from SZ patient iPSC-derived neural progenitor cells compared to control cells (Brennand et al. 2015. Molecular Psychiatry. 20: 361-368).
In addition to previously identified pathways, Literature Lab™ PLUS identified pathways associated with the mature stage of the disease, as well as several emerging and unanticipated pathway associations, thereby offering insight into the neurodevelopmental stage of the disease.
Breast cancer metastasis
In honor of Breast Cancer Awareness month, we analyzed several gene signatures associated with breast cancer metastasis using the Literature Lab™ platform.
We first analyzed the landmark paper by van't Veer et al. (Nature 415, 530-536 (31 January 2002)) and the 70-gene signature prognostic for metastasis in breast tumor cells. The results provide a modern perspective on pathway associations based on the current content of PubMed and Literature Lab™ analytics. Next, we compared this gene signature to those linked with target organ metastasis including lung and bone. This analysis identified several specific pathways and unexpected results that may lead to novel lines of investigation.
Literature Lab™ interrogation of gene sets relevant to gastric cancer: Comparison to NCI-Pathway Interaction Database based analysis.
The study by The Cancer Genome Atlas Network (Nature 513, 202–209 (11 September 2014) doi:10.1038/nature13480) identified gene sets used in the characterization of the four gastric cancer subtypes. An interaction pathway analysis method based on the NCI-Pathway Interaction Database was used to gauge the strength of gene set pathway associations.
Literature Lab™ PLUS gene set comparisons and pathway analyses found similarities with the NCI-PID method in the paper. However, important differences were identified which may lead the way to interesting untapped lines of investigation. Comparisons and contrasts between the two methods are discussed.
MS and autoimmune disorders
Literature Lab™ PLUS analysis of key associations, and comparisons between existing and novel gene sets linked to Multiple Sclerosis.
Literature Lab™ analyses of gene variants identified in genome wide association studies of Multiple Sclerosis. In a study by the International Multiple Sclerosis Genetics Consortium (IMSGC) (Nat Genet. 2013 Nov; 45(11): 10.1038/ng.2770), the ImmunoChip custom genotyping array was used to identify 48 new non-MHC susceptibility variants, which were analyzed along with a high resolution Bayesian fine-mapping variant gene set, and the previously known non-MHC gene set.
The Literature Lab™ results show associations with MS and autoimmune disorders in general, however, interesting associations with various forms of cancer and infectious diseases shed light on potential novel lines of investigation.
Differential regulation of gene expression in response to treatment between patients and controls.
A bioinformatics expert at a major research university was asked to analyze data from a time course experiment on 7 patients. He found that he needed to “push” the data in order to see differential gene expression activity. The data proved to be uniform, and many small changes were observed to be operating in a coordinated fashion. However, standard enrichment analysis tools were unable to provide useful information about the functional roles of the gene sets.