Preprint Article Version 1 This version is not peer-reviewed

BioSearch Engine Design : R Code elucidation into the mechanics of search engine that reveals unexplored/ untested combinatorial biological hypotheses in silico, using ETC-1922159 data.†

Version 1 : Received: 25 September 2018 / Approved: 26 September 2018 / Online: 26 September 2018 (10:59:30 CEST)

How to cite: Sinha, S. BioSearch Engine Design : R Code elucidation into the mechanics of search engine that reveals unexplored/ untested combinatorial biological hypotheses in silico, using ETC-1922159 data.†. Preprints 2018, 2018090507 (doi: 10.20944/preprints201809.0507.v1). Sinha, S. BioSearch Engine Design : R Code elucidation into the mechanics of search engine that reveals unexplored/ untested combinatorial biological hypotheses in silico, using ETC-1922159 data.†. Preprints 2018, 2018090507 (doi: 10.20944/preprints201809.0507.v1).

Abstract

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. Currently, a major persisting problem is to cherry pick the combinations based on expert advice, literature survey or guesses for investigation. This entails investment in time, energy and expenses at various levels of research. To address these issues, a search engine design was recently been developed, which showed promise by revealing existing confirmatory published wet lab results. Additionally and of import, the engine mined up a range of unexplored/untested/unknown combinations of genetic factors in the Wnt pathway that were affected by ETC-1922159 enantiomer, a PORCN-WNT inhibitor, after the colorectal cancer cells were treated with the inhibitor drug. As an example, MYC is known to upregulate PRC2 complex. PRC2 complex contains EZH2, which suppresses tumor suppressor genes via epigenetic modifications. MYC and HOXB8 are up regulated in colorectal cancer, however, the dual working mechanism of the same is not known. The in silico engine showed positioning which correctly approximates and assigns to this 3rd order combination of MYC-HOXB8-EZH2, pointing to the in vitro/in vivo down regulation by ETC-1922159. If the protein interaction of MYC-HOXB8 can be established and a study be done apropos EZH2, it will establish at in vitro/in vivo level, the in silico ranking also. The potential of this engine is immense given the problem faced in biology and other fields. Here we elucidate the R code to understand the mechanics of the search engine in a fluid manner for systems biologists. Though the search engine is in the developmental stage, we share the detailed mechanism of the working principles of the same as it can be generalized to problems in other fields.

Subject Areas

BioSearch Engine Designm, ETC-1922159, Ranking, Combinatorial forest space, Sensitivity analysis, Support Vector Machine, Colorectal Cancer

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