In silico characterization of hypothetical proteins from Paracoccidioides lutzii

Abstract

ABSTRACT. Nearly 60% of Paracoccidioides lutzii genes encode products annotated as hypothetical or predicted proteins (HPs). In this study, we describe the global detection and functional inference of HPs, using computational methods based on sequence similarity, identification of targeting signals, presence of known protein domains, and use of the Gene Ontology functional classification scheme. Our analysis enabled a highthroughput characterization of predicted cellular localization and presence of protein domains, clustering HPs into different functional categories including metabolism, localization, cell cycle, response to stimulus, and signaling. To investigate P. lutzii HP expression profiles, we used data obtained from the expressed sequence tag database (dbEST). These analyses revealed 2364 HPs expressed in different situations, namely in mycelial and yeast forms, during the transition from mycelium to yeast, and under conditions mimicking infection. Based on this transcriptomic data, we performed a functional enrichment analysis according to the domains present in the HPs expressed in each condition. The most overrepresented functional domains were those involved in the regulation of gene expression, suggesting important and as yet undescribed roles 17417 Hypothetical proteins from Paracoccidioides lutzii ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 17416-17425 (2015) for these HPs in the adaptation of P. lutzii to environmental conditions. In addition, the expression profiles of six randomly selected HPs were analyzed by quantitative real-time polymerase chain reaction in order to verify their expression in the complementary DNA libraries analyzed in this investigation. The approach used in this study should improve functional characterization of P. lutzii HPs.

Proteomic analysis of Paracoccidioides brasiliensis complex isolates: Correlation of the levels of differentially expressed proteins with in vivo virulence

“…In fact, Desjardins et al . [57] reported that nearly 60% of Paracoccidioides genes were annotated as those encoding hypothetical proteins with unknown cellular functions, but for which no evidence of in vivo expression exists [112]. To the best of our knowledge, this is the first report describing the role of such a protein in Paracoccidioides -induced mouse infection.…”

ParaDB: A manually curated database containing genomic annotation for the human pathogenic fungi Paracoccidioides spp.

“…Databanks dedicated to the storage of genomic data from Paracoccidioides spp. started to be designed since the pioneering EST analyses conducted with isolate Pb18 [12,13] and the information provided by these datasets greatly assisted the scientific community in a large number of projects, which contributed to improve our knowledge about this important group of human pathogenic fungi (recently reviewed by [49,50]). However, these original EST databases were gradually abandoned or deactivated after the release of the first draft genomes obtained for isolates Pb18, Pb03 and Pb01 [17].…”

Challenges in Serologic Diagnostics of Neglected Human Systemic Mycoses: An Overview on Characterization of New Targets

“…It is particularly important to highlight the potential role of hypothetical proteins in the infection process [ 257 ] and in vaccine development [ 258 ], as well as their role as diagnosis markers [ 43 ], drug targets [ 259 ], and in understanding physiological and biochemical pathways [ 257 , 260 , 261 ]. The analysis of these proteins is frequently neglected because of the absence of functional information.…”