GrowMatch: An Automated Method for Reconciling In Silico/In Vivo Growth Predictions
نویسندگان
چکیده
Genome-scale metabolic reconstructions are typically validated by comparing in silico growth predictions across different mutants utilizing different carbon sources with in vivo growth data. This comparison results in two types of model-prediction inconsistencies; either the model predicts growth when no growth is observed in the experiment (GNG inconsistencies) or the model predicts no growth when the experiment reveals growth (NGG inconsistencies). Here we propose an optimization-based framework, GrowMatch, to automatically reconcile GNG predictions (by suppressing functionalities in the model) and NGG predictions (by adding functionalities to the model). We use GrowMatch to resolve inconsistencies between the predictions of the latest in silico Escherichia coli (iAF1260) model and the in vivo data available in the Keio collection and improved the consistency of in silico with in vivo predictions from 90.6% to 96.7%. Specifically, we were able to suggest consistency-restoring hypotheses for 56/72 GNG mutants and 13/38 NGG mutants. GrowMatch resolved 18 GNG inconsistencies by suggesting suppressions in the mutant metabolic networks. Fifteen inconsistencies were resolved by suppressing isozymes in the metabolic network, and the remaining 23 GNG mutants corresponding to blocked genes were resolved by suitably modifying the biomass equation of iAF1260. GrowMatch suggested consistency-restoring hypotheses for five NGG mutants by adding functionalities to the model whereas the remaining eight inconsistencies were resolved by pinpointing possible alternate genes that carry out the function of the deleted gene. For many cases, GrowMatch identified fairly nonintuitive model modification hypotheses that would have been difficult to pinpoint through inspection alone. In addition, GrowMatch can be used during the construction phase of new, as opposed to existing, genome-scale metabolic models, leading to more expedient and accurate reconstructions.
منابع مشابه
in silico screening of IL-1β production inhibitors using chemometric tools
The IL-1β play a major role in inflammatory disorders and IL-1β production inhibitors can be used in the treatment of inflammatory and related diseases. In this study, quantitative relationships between the structures of 46 pyridazine derivatives (inhibitors of IL-1β production) and their activities were investigated by Multiple Linear Regression (MLR) technique Stepwise Regression Method (ES-S...
متن کاملin silico screening of IL-1β production inhibitors using chemometric tools
The IL-1β play a major role in inflammatory disorders and IL-1β production inhibitors can be used in the treatment of inflammatory and related diseases. In this study, quantitative relationships between the structures of 46 pyridazine derivatives (inhibitors of IL-1β production) and their activities were investigated by Multiple Linear Regression (MLR) technique Stepwise Regression Method (ES-S...
متن کاملI-1: Screening of Subfertile Men for Testicularlar Carcinoma In Situ by An Automated Image Analysis-Based Cytological Test of The Ejaculate
Background: Testicular cancer (TC) is usually diagnosed after manifestation of an overt tumour. Tumour formation is preceded by a pre-invasive and asymptomatic stage, carcinoma in situ (CIS) testis, except for very rare subtypes. The CIS cells are located within seminiferous tubules but can be exfoliated and detected in ejaculates with specific CIS markers. Materials and Methods: We have built ...
متن کاملPredicting Population for Male of Rural Area in Bangladesh
In this paper the population for male of rural area in Bangladesh is predicted by using the geometric growth rate method. The predictions are computed in a three-step procedure. In the first step, the prediction are computed using an exponentail model estimated by Quasi-Newton method for the years 1974, 1981, 1991, and 2001 using the package STATISTICA. Using the cross-validation predicti...
متن کاملStructure Evaluation of IroN for Designing a Vaccine against Escherichia Coli, an In Silico Approach
Introduction: Some strains of Escherichia Coli, including intestinal pathogenic strains, commensal strains, and extra intestinal pathogenic E. coli (ExPEC) have a significant impact on human health status. A standard vaccine designed based on conserved epitopes can stimulate a protective immune response against these pathogens. Additionally, enhanced expression at the infection site as a pathog...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- PLoS Computational Biology
دوره 5 شماره
صفحات -
تاریخ انتشار 2009