Evaluación de la calidad educativa de medicina y odontología

The primary unit of data used in PTM-Switchboard is a three-way interaction—

the MFG triplet—as described in Chapter 1 and illustrated in Figure 1.2. The database currently contains 519 fully characterized and experimentally validated MFG triplets. These triplets cover a total of 14 modifying enzymes and 15 TFs (Table 2.2), targeting 212 genes in 17 cellular contexts, and are derived from 69 different literature and knowledge base references. Each MFG triplet is stored un- der the data schema1 _{shown in Table 2.1. As noted in Chapter 1, the MFG triplet}

representation allows the effect of a modifying enzyme to be defined for each of a TF-Genes interaction individually, rather than uniformly across all TF targets. Therefore, multiple triplets contained in the database may share one or two mem- bers. For example, Hog1 regulates the overall transcriptional activity of Sko1 at a set of target gene promoters, and a separate triplet is included for each target.

The schema shown in Table 2.1 includes descriptive biological information about each MFG triplet, in addition to the identifiers for each gene member. The modifier can either have a positive or negative effect on the activity of the TF, and likewise the TF can be an activator or repressor of each target gene. In some especially complex cases, such as Sko1, the TF can act as both an activator and a repressor, depending on the activity of the modifying enzyme— in this case, kinase Hog1 [161]. To describe the behavior in such cases, the overall activity of the triplet is described by the influence of the TF on the target gene (positive, negative or neutral) in both the cases when the modifying enzyme is active and when the modifying enzyme is inactive. For example, in Figure 1.2 the relationship between F and G is neu- tral when M is inactive, and positive when M is active. Note that this is still a 1_{PTM-Switchboardis implemented using the MySQL database engine: http://www.mysql.com}

Field Description

mod name SGDofficial gene name for the modifying enzyme in the triplet

mod orfid SGDsystematic ORF ID for the modifying enzyme

mod class Class/type of modifying enzyme, e.g., “Kinase”

tf name SGDofficial gene name for the TF in the triplet

tf orfid SGDsystematic ORF ID for the TF

gene name SGDofficial gene name for the target gene

gene orfid SGDsystematic ORF ID for the target gene

ptm ids List of individual PTM sites (Table 2.3) that have been mapped for this par- ticular TF-Modifier interaction, each with indicator of whether the modifier adds or removes the PTM.

context ids List of cellular contexts in which triplet is known to function

ref ids List of literature and external database references containing evidence for this triplet

mod low Describes the interaction between the TF and target gene when the mod- ifier activity is low. A ‘+’ value indicates the TF promotes target gene expression, ‘-’ indicates the TF represses target gene expression, and ‘0’ indicates a disruption of the regulatory interaction between TF and target gene.

mod high Describes the interaction between the TF and target gene when the modifier activity is high. Possible values are the same as formod low.

evidence Evidence codes (Table 2.4) indicating the types of evidence found in support of the triplet from all references

Table 2.1: Schema for storing MFG triplets in PTM-Switchboarddatabase. Each triplet record is stored with all fields listed here.

simplification of complex dynamics, and is intended to serve as a primer for more quantitative investigations.

PTM-Switchboardspecifically focuses on MFG triplets involving a direct catal- ysis of a TF-PTM by a modifying enzyme, and does not include other types of regulatory triplets or cases that lack evidence for direct catalysis. Furthermore, the PTM must be relevant to TF activity at the promoter of the included target gene. This basic unit is an essential building block for more advanced studies of kinetics and fine-scale regulation at both the transcriptional and post-transcriptional level.

Modifiers

CDC34 FUS3 HOG1 HYR1 KSS1 MET30 OTU1 RSP5 SLT2 TPK1

TPK2 TPK3 UFD2 YPD1

Transcription Factors

FLO8 HOT1 MET4 MSN2 MSN4 OPI1 RLM1 SFL1 SKN7 SKO1 SMP1 SPT23 STE12 YAP1

Table 2.2: Unique Modifers and TFs included inPTM-Switchboard, listed bySGDgene symbols.

Field Description

ptm type The type of modification, e.g., phosphorylation

prot name TheSGDofficial gene name for the protein that is modified

prot orfid TheSGDsystematic ORF ID for the protein that is modified

prot refseq TheRefSeqaccession of the translated protein sequence

ptm pos The position of the modified amino acid (in the officialRefSeqsequence)

ptm res The single character abbreviation of the amino acid that is modified, e.g., ‘Y’ for tyrosine

context ids List of contexts in which the PTM has been observed

ref ids List of literature and external database references containing evidence for this PTM.

Table 2.3: Schema for storing PTMs inPTM-Switchboarddatabase. Each record with this schema corresponds to a unique modification site on a particular yeast protein.

Each unique PTM site (when mapped) is stored separately, according to the schema in Table 2.3. This table records each PTM at a specific residue of a TF protein, but independent of the modifying enzyme responsible. The same PTM can be involved in multiple MFG triplets, and likewise an MFG triplet can involve multiple PTMs. MFG triplets can involve both addition and removal of a chemical group. Even in the well-studied cases, the exact positions of the PTMs often have not been mapped.

However, PTM-Switchboardprovides a framework to store these PTMs as they are