**3.3 Manual curation**

Curation of model is time taking and tedious task that require special consideration during performance. It concentrates on re-evaluation and refinement of model content manually instead of mechanically. The reason behind the manual curation is the absence of proper and complete annotation of gene and their functions. In addition, the available database provides the information which is not organism specific. Consequently, there is a chance of adding those genes or reactions or metabolites which might not be the part of organism's metabolic network and affect the expected behavior of modeled organism. Thus, it is suggested to curate and assemble the draft model in pathway to pathway manners using KEGG, Gene Ontology, Candida Genome Database, UniProt and DrugBank that ultimately facilitate the detection of gaps of the model [42–45]. Moreover, the stage also includes the metabolic function verification, removal of generic reaction terms (protein, electron acceptor/donor, DNA, RNA *etc.*), addition of charged formula of each metabolite, inspection of reaction stoichiometry as well as directionality, localization of gene with its related reactions, association of gene-protein-reaction, append of transport reaction with literature support. Other than this, inclusion of sink reaction, demand reaction, growth associated and non-growth associated ATP maintenance reaction are also required in a model for *in-silico* growth of the organism (**Figure 4, step: 9)**.

#### **Figure 5.**

*Genome-Scale Metabolic Model of* C. albicans*. (A) Construction of model using Pathway Tools generated the detailed chromosome-wise description and (B) cellular overview of the model that defines the linkage among the metabolic pathways present in model. (C) For manual curaion, sbml format of model is converted to mathematical model which further subjected for evaluation and validation.*
