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Bioinformatics 2
“My main problem these days is that
I don’t understand how we go from
an experiment in the lab to a number
on the screen…”
Prof. XXX, CBE, FRS, FRSE
Sanguinetti, 2012
Bio2 lecture 1
Lecture 1
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Course Overview & Assessment
Introduction to Bioinformatics Research
Careers and PhD options
Core topics in Bioinformatics
– the central dogma of molecular biology
Sanguinetti, 2011
Bio2 lecture 1
About us...
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Degree in Physics
PhD in Mathematics (mathematical physics)
Got interested in mathematical modelling
Worked in machine learning &
bioinformatics & systems biology
• Office in forum, IF 1.44
• Shahzad Asif – finishing PhD student – lab
(week 5)
Sanguinetti, 2011
Bio2 lecture 1
Course Outcomes
• An appreciation of statistical methods in
bioinformatics, with special focus on
networks and probabilistic models
• Experience in using and/or implementing
simple solutions
• Appreciate the current ‘state of the art’
• Be familiar with some available resources
Sanguinetti, 2011
Bio2 lecture 1
Course Design
• Lectures cover (selective) background/
general concepts
• Guest lectures present current research/
applications of data analysis
• Self-study and assignments designed to
cover practical implementation
• Lab to give hands on experience support
Sanguinetti, 2011
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Guest lectures and topics
Donald Dunbar (Centre for Inflammation Research)
Transcriptomic technologies, week 4 (08/02)
Ian Simpson (School of Informatics)
ChIP technologies, week 8 (07/03)
Chris Larminie (GlaxoSmithKline)
Bioinformatics in the Pharmaceutical Sector, week 9 (14/03)
Sanguinetti, 2011
Bio2 lecture 1
Assessment (Bio2)
• Written assignment (released on 24/02, due
10/03)
– Data analysis mini project
– Plagiarism will be refereed externally
• Cite all sources!!!
– Late submissions get 0 marks!
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Bio2 lecture 1
Bioinformatics?
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Introduce yourselves to each other.
What is Bioinformatics?
What does Bioinformatics do for CS?
What does Bioinformatics do for Biology?
What guest Bioinformatics lecture would you
like?
• Discuss in groups for 10 min.
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Bio2 lecture 1
Answers
Sanguinetti, 2011
Bio2 lecture 1
What is BioInformatics?
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Sequence analysis and genome building
Molecular Structure prediction
Evolution, phylogeny and linkage
Automated data collection and analysis
Simulations and modelling
Biological databases and resources
Sanguinetti, 2011
Bio2 lecture 1
BioInf and CS
• Provides CS with new challenges with clear
bio-medical significance.
• Complex and large datasets sometimes very
noisy with hidden structures.
• Can biological solutions be used to inspire
new computational tools and methods?
Sanguinetti, 2011
Bio2 lecture 1
BioInf and Biology
• High-throughput biology:
– around 1989, the sequence of a 1.8kb gene
would be a PhD project
– by 1993, the same project was an undergraduate
project
– in 2000 we generated 40kb sequence per week
in a non-genomics lab
– Illumina/Solexa systems Gigabases per expt.
Sanguinetti, 2011
Bio2 lecture 1
Bioinformatics
• http://www.bbsrc.ac.uk/science/grants/index.html
– Awarded grants database
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http://bioinformatics.oxfordjournals.org
www.biomedcentral.org/bmcbioinformatics
www.nature.com/msb
http://bib.oxfordjournals.org/
Sanguinetti, 2011
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Bioinformatics@ed
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Database integration
Data provenance
Evolutionary and genetic computation
Gene expression databases
High performance data structures for semistructured data (Vectorised XML)
1/2
Sanguinetti, 2011
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Bioinformatics@ed
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Machine learning
Microarray data analysis
Natural language and bio-text mining
Neural computation, visualisation and
simulation
• Protein complex modeling
• Systems Biology
• Synthetic Biology
Sanguinetti, 2011
Bio2 lecture 1
2/2
Career Options
• Academic Routes
– Get Ph.D, do Postdoctoral Research lectureship and independent group
– M.Sc. RA - becomes semi independent usually
linked to one or more academic groups. Career
structure is less defined but improving. RAs
can do Ph.D. part-time.
Sanguinetti, 2011
Bio2 lecture 1
Career Options
• Commercial Sector
– Big Pharma - Accept PhD and MSc entry.
Normally assigned to projects and work within
defined teams. Defined career structure (group
leaders, project managers etc)
– Spin-out/Small biotech - Accept PhD and MSc
entry. More freedom and variety. A degree of
‘maintenance’ work is to be expected.
Sanguinetti, 2011
Bio2 lecture 1
Bioinformatics 2
Basic biology and roadmap
Sanguinetti, 2011
Bio2 lecture 1
How do you characterise life?
Sanguinetti, 2011
Bio2 lecture 1
The central “dogma” of
molecular biology
• Static genetic information is stored in DNA
• Genes are portions of DNA which are
“transcribed” into mRNA
• mRNA is “translated” by ribosomes into
proteins
• Proteins carry out the essential cellular
functions: enzymatic, regulatory, structural
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Slide from http://www.nd.edu/~networks/
GENOME
protein-gene
interactions
PROTEOME
protein-protein
interactions
Cell structure
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Metabolism
Bio2 lecture 1
Multiple control points
• DNA replication is regulated
• mRNA transcription is regulated by
transcription factor proteins
• mRNA degradation is regulated by RNA
binding proteins/ small RNAs
• mRNA translation is regulated by tRNA
• Enzymes “regulate” metabolism
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Multiple data types
• Sequencing (deep) measures genomic data
• Microarrays (lecture 3), PCR, RNA-seq
measure mRNA
• Flow cytometry/ fluorescence measures
single cell protein abundance
• Mass spectrometry measures proteins/
metabolites
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Multiple data types
• Chromatin immunoprecipitation measures
protein binding (lecture 8)
• Yeast 2 hybrid measures protein
interactions
• Nuclear magnetic resonance measures
metabolites
Sanguinetti, 2011
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Roadmap
• Lectures 1, 2, 3, 6 aim at covering basic
statistical/ ML tools to handle diverse data
types
• Guest lectures 4, 7, 8 illustrate particular
experimental tools and industrial apps
• Tutorials help clarifying concepts and
applying to problems
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Bio2 lecture 1