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#1 Pendahuluan
#1 Pendahuluan
#1 Pendahuluan
1
What is Bioinformatics?
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3
NIH – definitions
What is Bioinformatics? - Research, development,
and application of computational tools and on molecular
approaches for expanding the use of biological,
medical, behavioral, and health data, including the
means to acquire, store, organize, archive, analyze,
or visualize such data.
5
NSF – mission statement
The present bottlenecks in bioinformatics include the education of
biologists in the use of advanced computing tools, the recruitment
of computer scientists into this evolving field, the limited
availability of developed databases of biological information, and
the need for more efficient and intelligent search engines for
complex databases.
6
NSF – mission statement
The present bottlenecks in bioinformatics include the education of
biologists in the use of advanced computing tools, the recruitment of
computer scientists into this evolving field, the limited availability
of developed databases of biological information, and the need for
more efficient and intelligent search engines for complex databases.
7
Molecular Bioinformatics
Molecular Bioinformatics involves the use
of computational tools to discover new
information in complex data sets (from the
one-dimensional information of DNA through
the two-dimensional information of RNA and
the three-dimensional information of proteins,
to the four-dimensional information of
evolving living systems).
8
Bioinformatics (Oxford English Dictionary):
9
The field of science in which biology, computer science and
information technology merge into a single discipline
Biologists
collect molecular data:
DNA & Protein sequences,
gene expression, etc.
Bioinformaticians
Study biological questions by
analyzing molecular data
Computer scientists
(+Mathematicians, Statisticians, etc.)
Develop tools, softwares, algorithms
to store and analyze the data.
10
The hereditary information of all living organisms, with the exception of some viruses,
is carried by deoxyribonucleic acid (DNA) molecules.
2 purines: 2 pyrimidines:
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Circular genome
Central dogma: DNA makes RNA makes Protein
Modified dogma: DNA makes DNA and RNA, RNA makes DNA, RNA
an Protein
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Amino acids - The protein building blocks
14
15
Any region of the DNA sequence can, in principle, code for six different amino acid
sequences, because any one of three different reading frames can be used to
interpret each of the two strands.
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Protein folding
A human Hemoglobin:
17
How does it all looks like on a computer monitor?
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A cDNA sequence
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A cDNA sequence (reading frame)
A protein sequence
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And, a whole genome…
ACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGG
GGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCT
ACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGC
CGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTC
AACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCT
CCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCT
TGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCG
GCACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCT
GGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGAC
CTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAAC
GCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGG
TCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGC
CTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTT
CTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGG
CGGCACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGC
CTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAG
ACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCA
ACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCC
GGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCAC
GCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGC
TTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTG
GGCGGCGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGG
ACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGT
GCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCC
ATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTG
AGTGGGCGGCACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAA
GGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACC
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ACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCG...
How big are whole genomes?
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What do we actually do with bioinformatics?
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Sequence assembly
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(next generation sequencing)
Genome annotation
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Molecular evolution
Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic
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Smith et al. (2009) Nature 459, 1122-1125
Analysis of gene expression
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Toledo and Bardot (2009) Nature 460, 466-467
Protein structure prediction
Protein docking
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Luscombe, Greenbaum, Gerstein (2001)
From DNA to Genome
Sanger sequences
Watson and Crick insulin protein
1955
DNA model
1960 Dayhoff’s Atlas
Sequence
alignment 1965 ARPANET
(early Internet)
1970
PDB (Protein
Sanger dideoxy
Data Bank) 1975 DNA sequencing
1980 PCR (Polymerase
GenBank database
Chain Reaction)31
1985
NCBI SWISS-PROT
database
FASTA 1990
Human Genome
Initiative
BLAST
EBI
1995
33
In 1965, Dayhoff gathered all the available
sequence data to create the first bioinformatic
database (Atlas of Protein Sequence and
Structure).
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Complete Genomes
as of August 2011:
Eukaryotes 37
Prokaryotes 1708
Total 1745
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What can we do with sequences and other type of molecular information?
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Open reading frames
Functional sites
Annotation
Structure, function
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CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG
CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA
CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC
AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA
AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA
TAT GGA CAA TTG GTT TCT TCT CTG AAT ......
.............. TGAAAAACGTA
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promoter TF binding site
Transcription
CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG
CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA
Start Site
CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC
AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA
AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA
TAT GGA CAA TTG GTT TCT TCT CTG AAT .................................
Identifying orthologs
Inferences on structure
and function
Comparative
genomics
Comparing functional sites
Inferences on regulatory
networks
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Similarity profiles
Xenopus CGSHLVEALYLVCGDRGFFYYPKIKRDIEQ
Bos CGSHLVEALYLVCGERGFFYTPKARREVEG
***************:***** ** :*::*
Xenopus AQVNGPQDNELDG-MQFQPQEYQKMKRGIV
Bos PQVG---ALELAGGPGAGGLEGPPQKRGIV
.**. ** * * *****
Xenopus EQCCHSTCSLFQLENYCN
Bos EQCCASVCSLYQLENYCN
**** *.***:******* 43
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Ultraconserved Elements in the
Human Genome
Gill Bejerano, Michael Pheasant, Igor Makunin, Stuart
Stephen, W. James Kent, John S. Mattick, & David Haussler
(Science 2004. 304:1321-1325)
There are 481 segments longer than 200 base pairs (bp) that
are absolutely conserved (100% identity with no insertions or
deletions) between orthologous regions of the human, rat, and
mouse genomes. Nearly all of these segments are also
conserved in the chicken and dog genomes, with an average of
95 and 99% identity, respectively. Many are also significantly
conserved in fish. These ultraconserved elements of the human
genome are most often located either overlapping exons in
genes involved in RNA processing or in introns or nearby genes
involved in the regulation of transcription and development.
Junk is real!
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Genome-wide profiling of:
• mRNA levels
• Protein levels
Co-expression of genes
and/or proteins
Functional
genomics
Identifying protein-protein
interactions
Networks of interactions
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Understanding the function of genes and other
parts of the genome
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Structural Assign structure to all
genomics proteins encoded in
a genome
49
Biological
databases
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Database or databank?
Initially
• Databank (in UK)
• Database (in the USA)
Solution
• The abbreviation db
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What is a Database?
Accession number: 1
First Name: Amos
Last Name: Bairoch
Course: Pottery 2000; Pottery 2001;
//
Accession number: 2
First Name: Dan
Last name: Graur
Course: Pottery 2000, Pottery 2001; Ballet 2001, Ballet 2002
//
Accession number 3:
First Name: John
Last name: Travolta
Course: Ballet 2001; Ballet 2002;
//
• Easy to manage: all the entries are visible at the same time !
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Database: a « relational » example
Relational database (« table file »):
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Some databases in the field of molecular biology…
EBI:
http://www.ebi.ac.uk/
DDBJ:
http://www.ddbj.nig.ac.jp/
61
Literature Databases:
Bookshelf: A collection of searchable biomedical books linked to
PubMed.
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A search by subject: “mitochondrion evolution”
Type in a Query term
• Enter your search words in the
query box and hit the “Go” button
http://www.ncbi.nlm.nih.gov/entrez/query/static/help/helpdoc.html#Searching
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The Syntax …
1. Boolean operators: AND, OR, NOT must be entered in
UPPERCASE (e.g., promoters OR response elements). The default
is AND.
3. Quotation marks: The term inside the quotation marks is read as one
phrase (e.g. “public health” is different than public health, which will
also include articles on public latrines and their effect on health
workers).
4. Asterisk: Extends the search to all terms that start with the letters
before the asterisk. For example, dia* will include such terms as 69
diaphragm, dial, and diameter.
Refine the Query
• Often a search finds too many (or too few) sequences, so you
can go back and try again with more (or fewer) keywords in
your query
• The “History” feature allows you to combine any of your past
queries.
• The “Limits” feature allows you to limit a query to specific
organisms, sequences submitted during a specific period of
time, etc.
• [Many other features are designed to search for literature in
MEDLINE]
70
Related Items
You can search for a text term in sequence annotations or in
MEDLINE abstracts, and find all articles, DNA, and protein
sequences that mention that term.
Then from any article or sequence, you can move to "related
articles" or "related sequences".
•Relationships between sequences are computed with BLAST
•Relationships between articles are computed with "MESH" terms
(shared keywords)
•Relationships between DNA and protein sequences rely on accession
numbers
•Relationships between sequences and MEDLINE articles rely on both
shared keywords and the mention of accession numbers in the articles.
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A search by authors: “Esser” [au] AND “martin” [au]
A search by title word: “Wolbachia pipientis” [ti]
Database Search Strategies
• General search principles - not limited
to sequence (or to biology).
• Start with broad keywords and narrow
the search using more specific terms.
• Try variants of spelling, numbers, etc.
• Search many databases.
• Be persistent!!
77
Searching PubMed
• Structureless searches
– Automatic term mapping
• Structured searches
– Tags, e.g. [au], [ta], [dp], [ti]
– Boolean operators, e.g. AND, OR, NOT, ()
• Additional features
– Subsets, limits
– Clipboard, history
78
Start working:
Search PubMed
1. cuban cigars
2. cuban OR cigars
3. “cuban cigars”
4. cuba* cigar*
5. (cuba* cigar*) NOT smok*
6. Fidel Castro
7. “fidel castro”
8. #6 NOT #7 79
“Details” and “History” in
PubMed
80
“Details” and “History” in
PubMed
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The OMIM (Online Mendelian
Inheritance in Man)
82
MIM Number Prefixes
* gene with known sequence
+ gene with known sequence and
phenotype
# phenotype description, molecular
basis known
% mendelian phenotype or locus,
molecular basis unknown
no prefix other, mainly phenotypes with
suspected mendelian basis
83
Searching OMIM
• Search Fields
– Name of trait, e.g., hypertension
– Cytogenetic location, e.g., 1p31.6
– Inheritance, e.g., autosomal dominant
– Gene, e.g., coagulation factor VIII
84
OMIM search tags
85
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Start working:
Search OMIM
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Online Literature databases
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Online Glossaries
Bioinformatics :
http://www.geocities.com/bioinformaticsweb/glossary.html
http://big.mcw.edu/
Genomics:
http://www.geocities.com/bioinformaticsweb/genomicglossary.html
Molecular Evolution:
http://workshop.molecularevolution.org/resources/glossary/
Biology dictionary:
http://www.biology-online.org/dictionary/satellite_cells
92
What is Google Scholar?
93
Use Google Scholar to find articles from a
wide variety of academic publishers,
professional societies, preprint repositories
and universities, as well as scholarly articles
available across the web.
94
Google Scholar
orders your
search results by
how relevant they
are to your query,
so the most
useful references
should appear at
the top of the
page
This relevance
ranking takes into
account the: full
text of each article.
the article's author,
the publication in
which the article
appeared and how
often it has been
cited in scholarly 95
literature.
What other DATA can we retrieve from the record?
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5. Google Book Search
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Start working:
101
6. Web of science
http://http://apps.webofknowledge.com.ezproxy.lib.uh.edu/WOS_GeneralSearch_input.do?product
=WOS&search_mode=GeneralSearch&SID=4FB7LbbLgDMhG9fDiLh&preferencesSaved=
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Strategi: penelitian kolaboratif
Contoh 1: Repositori dan Genome Browser
Pengetahuan Departemen
yang diperlukan terkait
Klasifikasi tumbuhan,
hewan
Peneliti Biologi
Pencarian/perancangan
obat, termasuk obat
Peneliti biokimia/ herbal
farmasi
Strategi: penelitian kolaboratif
Contoh 2 : Sistem Pengidentifikasi SNP
Pengetahuan Departemen
yang diperlukan terkait
Agronomi,
Pemuliaan, Tek
Pertanian
Multiple Sequence
Alignment dengan
Dynamic Ilmu Komputer
Programming, (Lab. IR, NCC
Parallel Computing Bioinformatika)
Strategi: penelitian kolaboratif
Contoh 3: DNA Sequence Assembly
Pengetahuan Departemen
yang diperlukan terkait
Karakteristik Biologi
sekuens DNA,
repeats, micro- Biokimia
satellite,
sequencing
error,
polymorphism
de Bruijn graph
Solusi dicapai
dengan
menemukan algoritme graf,
struktur data, Matematika
Eulerian Path
dynamic
programming Ilmu Komputer
Consensus (Lab. Information
dilakukan Retrieval,
dengan Multiple Bioinformatika)
Alignment
DNA Sequence Assembly
Selayang pandang proses pembacaan seluruh genom dengan teknik shotgun.
Potongan
DNA genom
Reads
Contigs
Scaffolds
Pemetaan
scaffolds
Peta genom
Perakitan urutan genom
Gambaran menyeluruh dari semua reads
yang saling bersambung dan membentuk Tampilan dekat: urutan basa
sebuah contig. dari contig yang terbentuk.
Binning
tanah
DNA Sequencing
http://www.eng.unimelb.edu.au
Clustering/machine Fisika
learning
kombinatorial, Statistika
geometri, quantum,
energi, pemodelan Matematika
dan simulasi,
grafika komputer, Ilmu Komputer (Lab.
high performance CI, IR, NCC, KDE,
computing SEIns Bioinformatika)
Capaian riset Departemen
Ilmu Komputer IPB
2016/4/5 113
PENGELOMPOKAN FRAGMEN
METAGENOM DENGAN
METODE GROWING SELF
ORGANIZING MAP
INTERSPECIES CHIMERAS
B
BINNING
KESALAHAN
PERAKITAN
116
Solusi Masalah
Environmental Sampels
BINNING
Firmicutes Proteobacteria
117
BINNING berdasarkan taksonomi Filum
Metagenome fragment binning – two main approaches
Homology based approach
• compare fragments against reference databases by sequence alignment
• assign taxon ID to each sequence based on the NCBI taxonomy
• summary the results at different taxonomy levels [Huson 2007]
DNA fragments
reference database
119
Growing Self Organizing Map
Evaluasi
Kombinasi Parameter terbaik pada frekuensi Spaced K-Mer dengan parameter Learning
Rate (LR) 0.5 dan Neighborhood Size (NS) 1
0.600
0.500
0.400 Titik Minimum
0.300
0.200
0.100
0.000
0 1 2 3 4
LR 0.1 0.813 0.807 0.822 0.819 0.789
Quantization Error
LR 0.25 0.842 0.816 0.827 0.827
Terkecil pada Learning
0.806
LR 0.5 0.823 0.665 0.746
Rate 0.5 dan0.803 0.798
LR 0.75 0.870 0.767 Neighborhood
0.806 Size 1
0.801 0.813
LR 0.9 0.818 0.776 dengan error0.801
0.811 0.665 0.786
LR 0.1 LR 0.25 LR 0.5 LR 0.75 LR 0.9
120
PENGEMBANGAN SISTEM IDENTIFIKASI DAN
ANALISIS SINGLE NUCLEOTIDE POLYMORPHISM
UNTUK PEMULIAAN
TANAMAN KEDELAI
Tim Peneliti:
Dr. Wisnu Ananta Kusuma (Ilmu Komputer, IPB)
Dr. Agus Buono (Ilmu Komputer, IPB)
Dr. Ir. I Made Tasman (BB Biogen)
Habib Rijzaani (BB Biogen)
Mukhlis Hidayat, M.Kom (Matematika, Unsyiah)
• Langkah-langkahnya :
A. Pairwise alignment
– Menghitung matriks jarak kemiripan
Luaran dan Capaian
(Lloyd 2010)
Paralelisasi pairwise alignment
• Matriks penjajaran dibagi secara blocked
columnwise
• Tiap prosesor menghitung isi matriks pada
kolom bagiannya masing-masing secara
pipelining
10-15 tahun