br Genetic mutation is one of the cancer gene
Genetic mutation is one of the cancer gene attributes, which aﬀects cell growth (Vogelstein and Kinzler, 2004). Like, cancer disease results from significant changes in amino Bafilomycin A1 sequence of tumor cells (Amoêdo et al., 2013). These amino acid contents dictate the spatial and biochemical properties of gene present in every living cell (Koolman and Rohm, 2005), lack of which can cause genetic disease, indigestion, neurological problems, etc. (Vaidyanathan, 2004).
The cancerous and non-cancerous genes can be distinguished ac-cording to their two important features i.e. polarity and length.
According to polarity, cancerous genes vary from being highly hydro-philic to totally hydrophobic (Kyte and Doolittle, 1982). According to length, the polar genes are generally smaller in size and contain large amounts of hydrophilic amino acids, and the nonpolar genes are larger in size and contain relatively larger amount of hydrophobic amino acids (Golub et al., 1999; Long et al., 2011; Parry et al., 2015).
In this paper, we address prediction of genetic disease related issues and realize gene network model by cascading individual amino acid circuit model. Since amino acid based modeling approach is proved to be more sensitive in designing nanobiosensors (McClellan, 2012), the proposed electrical gene sensor model is the suitable choice regarding nanotechnology and nanobioscience based treatment. Properties like ‘hydrophilicity or hydrophobicity and gene size or length (number of amino acids)’ are the key features to study the genetic attributes of cancer cell. The main objectives of this paper are following:
• Model equivalent electrical circuit using passive electrical compo-nents resistor, capacitor and inductor for individual amino acid, based on hydropathy index value.
• Cascade amino acid circuit model using 1st Foster topology (Daryanani and Resh, 1969) to realize electrical gene sensor model.
• Investigate the electrical responses to predict attributes of cancerous and non-cancerous genes which are downloaded as soft databases from public domain (http://www.ncbi.nlm.nih.gov; http://cgap.nci.
Abbreviations: DNA, deoxyribonucleic acid; RNA, ribonucleic acid; NCBI, National Center for Biotechnology Information; CGAP, cancer genome anatomy project; R, resistor; C, capacitor; L, inductor; MCC, Matthews correlation coeﬃcient; RL, load resistance; TP, true positive; TN, true negative; FP, false positive; FN, false negative; ROC, region of convergence
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List of hydrophobic, hydrophilic amino acids and their corresponding circuit element.
Amino acid type Amino acid name Hydropathy Side chain circuit
nih.gov; http://www.genecards.org). • Finally, establish putative connection between electrical responses and biological attributes of actual genes.
The methodology of gene sensor modeling is described in this sec-tion. Electrical circuit model for individual amino acid using passive electrical components is illustrated in Section 2.1. Realization of gene network by cascading equivalent amino acid circuit model is depicted in Section 2.2. In Section 2.3, electrical sensor for detecting gene is
realized as prediction tool to distinguish cancer and non-cancer cells.
2.1. Individual amino acid circuit model realization
Amino acids are the molecules, containing an amino group (NH2), a carboxylic acid group (COOH), and a side chain (r) group. The equivalent electrical model for individual amino acid consists of back-bone model (i.e. carboxyl and amino group), and the side chain model. This side chain model is connected in parallel with the backbone model. The choice of circuit elements is governed by the amino acid backbone and side chain. The backbone is constant for all amino acids except Proline and represented by resistor Rb of 7 Ω as the structure comprised of total seven atoms i.e. 4 atoms from COOH and 3 atoms from NH2, whereas ‘Proline’ backbone structure is represented through resistor R of 6 Ω as amino group (NH) has 2 atoms.
Amino acids have variable side chain group, and they are classified into groups of hydrophilic and hydrophobic based on its side chain hydropathy index values. The side chains of hydrophobic and hydro-philic amino acids are represented by inductor LSC and capacitor CSC respectively. The values of circuit elements representing side chains are chosen based on hydropathy index value (Kyte and Doolittle, 1982) of side chain (Table 1).
The equivalent impedance expression for the amino acid electrical model is expressed as follows,
For hydrophobic amino acid, the equivalent impedance ZHb is,