Difference between revisions of "HMM"

Revision as of 18:48, 11 September 2015

We use HMMs to detect phosphatase domains and accessory domains. We benefit from the HMMs in public database such as Pfam, and the sequence alignments from public database such as CDD, SMART and COG, which are useful to build HMMs. We also build HMMs from scratch.

List of HMMs of phosphatase domains

AP_AP

CC1_DSP

CC1_Myotubularin

CC1_OCA

CC1_PTEN

CC1_PTP

CC1_Paladin

CC1_Sac

CC2_LMWPTP

CC2_SSU72

HAD_EYA

HAD_FCP

HAD_NagD

HP_HP1

HP_HP2

PHP_PHP

PPM_PPM

PPPL_PAP

PPPL_PPPc

RTR1_RTR1

Rhodanese_CDC25

List of HMMs of accessory domains

PAP_NTD: in-house HMM of Purple Acid Phosphatase, N-Terminal Domain

CDC25_NTD: in-house HMM of CDC25, N-terminal domain

IQ: built from SMART alignment

PPIP5K_RimK

STS_UBA

MTMR5_C1: in-house HMM of MTMR5, C1 domain

MTMR_GRAM: in-house HMM of myotubularin, GRAM domain

PP2C_C: Pfam HMM specifically matches with PPP1C but not other PPP subfamilies

The Pfam PP2C_C profile only match to PPP1C subfamily, but not other PPPc subfamilies. It overlaps with our in-house PPPc HMM profile.

Guidance for HMM building

We usually built the HMMs from PSI-BLAST hits.

To find the domain sequences for building a HMM, we PSI-BLASTed the domain sequence or the full sequence usually against protein NR dataset via NCBI BLAST server. It sometime matters if you query the region that is supposed to contain the domain (based upon structure or any evidence) or the full sequence. The full sequence is often more sensitive to find weak hits to the domain. We recommended to download the files of Alignment, Search Strategies, and PssmWithParameters of PSI-BLAST result for reproductivity.

After several rounds of PSI-BLAST, we download the sequences of the aligned regions (not the complete sequences) from PSI-BLAST result. Because some sequences are redundant, which are not useful to build the HMM profile, we create the non-redundant sequence data set by using program CD-HIT (usually with sequence identity threshold as 70%, i.e. the parameter -c is set as 0.7).

We then carry out multiple sequence alignment (MSA) using programs such as MUSCLE, manually adjust the alignment usually by removing low-quality region in MSA editor such as JalView. We further inspect the distribution of sequence lengths in the MSA and remove the sequences which are shorter than most sequences in the MSA. How we remove the short sequences is dependent on the distribution and the MSA itself, which varies case by case.

We carry out MSA program and manually adjust the resulted MSA again after remove the short sequences. Then, we build HMM using program HMMBUILD. Depending on the format you use, you may need to convert the MSA into STOCKHOLM format before running HMMBUILD.