Applying a Gene Reversal Rate Computational Methodology to Identify Drugs for a Rare Cancer: Inflammatory Breast Cancer.

The aim of this study was to utilize a computational methodology based on Gene Reversal Rate (GRR) scoring to repurpose existing drugs for a rare and understudied cancer: inflammatory breast cancer (IBC). This method uses IBC-related gene expression signatures (GES) and drug-induced gene expression profiles from the LINCS database to calculate a GRR score for each candidate drug, and is based on the idea that a compound that can counteract gene expression changes of a disease may have potential therapeutic applications for that disease. Genes related to IBC with associated differential expression data (265 up-regulated and 122 down-regulated) were collated from PubMed-indexed publications. Drug-induced gene expression profiles were downloaded from the LINCS database and candidate drugs to treat IBC were predicted using their GRR scores. Thirty-two (32) drug perturbations that could potentially reverse the pre-compiled list of 297 IBC genes were obtained using the LINCS Canvas Browser (LCB) analysis. Binary combinations of the 32 perturbations were assessed computationally to identify combined perturbations with the highest GRR scores, and resulted in 131 combinations with GRR greater than 80%, that reverse up to 264 of the 297 genes in the IBC-GES. The top 35 combinations involve 20 unique individual drug perturbations, and 19 potential drug candidates. A comprehensive literature search confirmed 17 of the 19 known drugs as having either anti-cancer or anti-inflammatory activities. AZD-7545, BMS-754807, and nimesulide target known IBC relevant genes: PDK, Met, and COX, respectively. AG-14361, butalbital, and clobenpropit are known to be functionally relevant in DNA damage, cell cycle, and apoptosis, respectively. These findings support the use of the GRR approach to identify drug candidates and potential combination therapies that could be used to treat rare diseases such as IBC.

Literature-Wide Association Studies (LWAS) for a Rare Disease: Drug Repurposing for Inflammatory Breast Cancer.

Drug repurposing is an effective means for rapid drug discovery. The aim of this study was to develop and validate a computational methodology based on Literature-Wide Association Studies (LWAS) of PubMed to repurpose existing drugs for a rare inflammatory breast cancer (IBC). We have developed a methodology that conducted LWAS based on the text mining technology Word2Vec. 3.80 million "cancer"-related PubMed abstracts were processed as the corpus for Word2Vec to derive vector representation of biological concepts. These vectors for drugs and diseases served as the foundation for creating similarity maps of drugs and diseases, respectively, which were then employed to find potential therapy for IBC. Three hundred and thirty-six (336) known drugs and three hundred and seventy (370) diseases were expressed as vectors in this study. Nine hundred and seventy (970) previously known drug-disease association pairs among these drugs and diseases were used as the reference set. Based on the hypothesis that similar drugs can be used against similar diseases, we have identified 18 diseases similar to IBC, with 24 corresponding known drugs proposed to be the repurposing therapy for IBC. The literature search confirmed most known drugs tested for IBC, with four of them being novel candidates. We conclude that LWAS based on the Word2Vec technology is a novel approach to drug repurposing especially useful for rare diseases.

[Changes of polyamines level in Glycine soja and Glycine max seedlings under NaCl stress].

With internationally common-used Glycine max (the salt-tolerant Lee68) and Glycine soja (the salt-sensitive N23232) as reference, this paper studied the polyamines (PAs) contents and polyamine oxidase (PAO) activities in the highly salt-tolerant BB52 (Glycine soja) seedlings, which showed that under 150mmol x L(-1) NaCl stress for 2d, the decrease of Put and Spd contents was more significant, but that of Spd content was less significant in roots of BB52 than in those of Lee68 and N23232. For leaves, the decrease of Put and increase of Spd contents were markedly observed in BB52. The ascent of (Spm + Spd)/Put ratios and descent of Put/PAs ratios showed a positive relation to their salt tolerance. The PAO activity in roots and leaves was all increased, and most obvious in N23232. The relationship between PAs levels in BB52 and its salt tolerance was also discussed.