Tools for BioInformatics

Eileen KraemerComputer Science Dept.The University of Georgia

Types of Tools

Lab samples

Production Sequencing Software

Sequence data Databases, Database Search Tools

Production Sequencing Software

used throughout the sequencing procedure from preparation of the DNA through to the finishing of clones.

Example: Sanger Centre,Shotgun Sequencing of typical human clone

Data collection Transfer to UNIX Gel image processing Sequence pre-processing DNA Fragment Assembly Editing Finishing Services Quality Control and Assesment

Databases

Swiss-Prot EMBLEntrezGDBGenBankGSDBPDB& more -- see links at:http://www.public.iastate.edu/~pedro/rt_1.html

Species-specific Databases

See: http://genetics.about.com for both: Non-human and human genome projects

Examples: PomBase is a compilation of data relating

to the organism Schizosaccharomyces pombe

Wormpep predicted proteins from the C. elegans genome sequencing project.

Annotation Tools

Annotation of sequences with info such as homologies to known genes, possible gene locations, gene signals such as promoters, etc.

Example: Genotator (Nomi Harris) -- developing a workbench for automatic sequence annotation and annotation viewing and editing. The goal is to run a series of sequence analysis tools and display the results in such a way that the various predictions can be compared, and researcher makes decision of what to include.

Database Software

ACEDB is an acronym for "A Caenorhabditis elegans DataBase". It can refer to a database and data concerning the nematode C. elegans, or to the database software alone.

Other groups may adapt existing, or create own. For example, David Hall’s workflow project at UGA for Neurospora

Types of Tools

Sequence

Structure Function

Gene Prediction

Caution: accuracy <= ~ 70%Good review: Snyder and Stormo,

(chapter 11 of the book Nucleic Acid and Protein Sequence Analysis: A Practical Approach, second edition, 1994. )

Gene Prediction

GRAIL(Xgrail, JavaGrail, etc.)GeneidNetgeneGenMarkFexon, Hexon GENSCANxpoundGenefinder (University of Washington)

GRAIL

Predicts coding regionsUses a neural network which combines a

series of coding prediction algorithms. recognizes coding potential within a fixed

size (100 base) window; evaluates coding potential without looking for additional features

later versions incorporate additional info human and other species

GeneMark

Based on inhomogeneous Markov models

predicts coding and non-coding regions based on statistical patterns in dinucleotide frequences … more next week from Mark B.

Sequence Alignment

Pairwise alignmentsMultiple sequence alignments

Pairwise Alignments

SIM (Protein only) - k best non-intersecting alignments (EXPASY)

ALIGN - optimal global alignment with no short-cuts (EERIE)

LALIGN - calculates the N-best local alignments (EERIE)

LFASTA - local similarity searches showing local alignments (EERIE)

BLAST 2 - local alignment using BLAST (NCBI) LAP2 - local DNA to protein alignment with LAP2 (MTU)

Multiple Sequence Alignments

ClustalW 1.7 (DNA/Protein) - Global progressive (BCM) CAP Sequence Assembly (DNA) - Contig Assembly MAP (DNA/Protein) - Global progressive in linear space PIMA 1.4 (Protein only) - Pattern-Induced (local) Multiple

Alignment (BCM) MSA 2.1 (Protein only) - Near-optimal sum-of-pairs global

(WashU) BLOCK MAKER (Protein only) - Finds conserved blocks in seq

sets (FHCRC)ClustalW 1.7 (DNA/Protein) - Global progressive (BCM)

MEME 2.2 (DNA/Protein) - Multiple EM for Motif Elicitation (SDSC)

Similarity Searching

BLAST -- (BLASTP, TBLASTN, etc.) a nucleotide or protein sequence sent to

the BLAST server is compared against and a summary of matches is returned to the user.

allows all combinations of DNA or protein query sequences with searches against DNA or protein databases:

BLAST variations

blastp compares an amino acid query sequence against a protein sequence database.

blastn compares a nucleotide query sequence against a nucleotide sequence database.

blastx compares the six-frame conceptual translation products of a nucleotide query sequence (both strands) against a protein sequence database.

tblastn compares a protein query sequence against a nucleotide sequence database dynamically translated in all six reading frames (both strands).

tblastx compares the six-frame translations of a nucleotide query sequence against the six-frame translations of a nucleotide sequence database.

Types of Tools

Sequence

Structure Function

Protein Structure Prediction

Ab initio -- based on energy minimizationfold recognition -- sequence -> secondary

structure, then align secondary structures with corresponding secondary structures in related proteins, etc.

statistical -- based on “hidden patterns”; similar patterns -> similar structure

Protein Secondary Structure Prediction

Coils - prediction of coiled coil regions nnPredict - uses a 2 layer neural networkPSSP / SSP - segment-oriented predictionPSSP / NNSSP - nearest-neighbor prediction SAPS - statistical analysis of protein sequencesPaircoil - coiled coil regions of pairwise residue

correlationsProtein Hydrophilicity /HydrophobicitySOPM - self optimized prediction method

Types of Tools

Sequence

Structure Function

Protein Function Prediction

Pfam - groups of similar function proteins

aligned and HMMs generated for each “cluster”

HMM generated for unknown function protein and compared to HMMs of known proteins for predicted function classification

Pfam components

PROTEIN HMM SEARCH - Analyze a protein query sequence to find Pfam domain matches.

DNA HMM SEARCH - Analyze a DNA query sequence to find Pfam domain matches. (Uses the GeneWise server at the Sanger Centre.)

BROWSE PFAM - View Pfam annotation and alignments.

TEXT SEARCH - Query Pfam by keywords.

BROWSE SWISSPFAM - View the domain organization of any SWISSPROT/TrEMBL sequence according to Pfam.

Types of Tools

Sequence

Sequence

Sequence

Sequence

Across organisms … Phylogeny Reconstruction

Phylogeny Reconstruction

Construct evolutionary trees based on divergences that occur in related sequences parsimony, minimum distance, etc. parsimony -- construct tree so that

number of mutation events is minimized PHYLIP, PAUP, others, some interactive

Visualization Tools

Database viewersSequence viewersMolecular viewers

Physical Mapping Software

used to physically locate genetic markers.

FPC Software for FingerPrinting Contigs.

Image 3.x Software for processing fingerprint gel images.

RHServer This web interface positions one or more markers on the 1998 International Gene Map (GB4).

SAM System for Assembling Markers. SAM takes as input a set of clones and their associated markers, and outputs a partially ordered marker map.

Z-RHMAPPER Extensions to the RHMAPPER (Whitehead) Radiation Hybrid Mapping Package.

Good Resources

Pedro’s BioMolecular Researchhttp://www.public.iastate.edu/~pedro/rt_1.html

BCM pageswww.hgsc.bcm.tmc.edu/SearchLauncher/index.html

Sanger Centerwww.sanger.ac.uk/Software/Sequencing/overview.shtml

Mining Co. Web Site genetics/miningco.com

& many others