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html (Bioinformatic
Introduction)
What is Bioinformatics?
1/5
!he "enomic era
!he "enomic era has seen a massi#e e$plosion in the amount of
biolo"ical information a#ailable due to hu"e ad#ances in the fields of
molecular biolo"% and "enomics.
Bioinformatics is the application of computer technolo"% to the mana"ement and anal%sis
of biolo"ical data. !he result is that computers are bein" used to "ather& store& anal%se
and mer"e biolo"ical data.
Bioinformatics is an interdisciplinar% research area that is the interface between the
biolo"ical and computational sciences. !he ultimate "oal of bioinformatics is to unco#er
the wealth of biolo"ical information hidden in the mass of data and obtain a clearer
insi"ht into the fundamental biolo"% of or"anisms. !his new knowled"e could ha#e
profound impacts on fields as #aried as human health& a"riculture& the en#ironment&
ener"% and biotechnolo"%.
'lease select a topic:
(h% is bioinformatics important)
Biolo"ical databases
Biolo"ical applications
*eal world applications of bioinformatics
(h% is bioinformatics important)
!he "reatest challen"e facin" the molecular biolo"% communit% toda% is to make sense of
the wealth of data that has been produced b% the "enome se+uencin" pro,ects.
!raditionall%& molecular biolo"% research was carried out entirel% at the e$perimental
laborator% bench but the hu"e increase in the scale of data bein" produced in this
"enomic era has seen a need to incorporate computers into this research process.
-e+uence "eneration& and its subse+uent stora"e& interpretation and anal%sis are entirel%
computer dependent tasks. .owe#er& the molecular biolo"% of an or"anism is a #er%
comple$ issue with research bein" carried out at different le#els includin" the "enome&
proteome& transcriptome and metabalome le#els. /ollowin" on from the e$plosion in
#olume of "enomic data& similar increase in data ha#e been obser#ed in the fields of
proteomics& transcriptomics and metabalomics.
!he first challen"e facin" the bioinformatics communit% toda% is the intelli"ent and
efficient stora"e of this mass of data. It is then their responsibilit% to pro#ide eas% and
reliable access to this data. !he data itself is meanin"less before anal%sis and the sheer
#olume present makes it impossible for e#en a trained biolo"ist to be"in to interpret it
manuall%. !herefore& incisi#e computer tools must be de#eloped to allow the e$traction
of meanin"ful biolo"ical information.
!here are three central biolo"ical processes around which bioinformatics tools must be
de#eloped:
012 se+uence determines protein se+uence
'rotein se+uence determines protein structure
'rotein structure determines protein function
!he inte"ration of information learned about these ke% biolo"ical processes should allow
us to achie#e the lon" term "oal of the complete understandin" of the biolo"% of
or"anisms.
Biolo"ical databases
Biolo"ical databases are archi#es of consistent data that are stored in a uniform and
efficient manner. !hese databases contain data from a broad spectrum of molecular
biolo"% areas. 'rimar% or archi#ed databases contain information and annotation of 012
and protein se+uences& 012 and protein structures and 012 and protein e$pression
profiles.
-econdar% or deri#ed databases are so called because the% contain the results of anal%sis
on the primar% resources includin" information on se+uence patterns or motifs& #ariants
and mutations and e#olutionar% relationships. Information from the literature is contained
in biblio"raphic databases& such as 3edline.
It is essential that these databases are easil% accessible and that an intuiti#e +uer% s%stem
is pro#ided to allow researchers to obtain #er% specific information on a particular
biolo"ical sub,ect. !he data should be pro#ided in a clear& consistent manner with some
#isualisation tools to aid biolo"ical interpretation.
-pecialist databases for particular sub,ects ha#e been set4up for e$ample 53B6 database
for nucleotide se+uence data& 7ni'rot8B/-wiss4'rot protein database and '0Be a 90
protein structure database.
-cientists also need to be able to inte"rate the information obtained from the underl%in"
hetero"eneous databases in a sensible manner in order to be able to "et a clear o#er#iew
of their biolo"ical sub,ect. -*- (-e+uence *etrie#al -%stem) is a powerful& +uer%in" tool
pro#ided b% the 5BI that links information from more than 15: hetero"eneous resources.
Biolo"ical applications
;nce all of the biolo"ical data is stored consistentl% and is easil% a#ailable to the
scientific communit%& the re+uirement is then to pro#ide methods for e$tractin" the
meanin"ful information from the mass of data. Bioinformatic tools are software pro"rams
that are desi"ned to carr% out this anal%sis step.
/actors that must be taken into consideration when desi"nin" these tools are:
!he end user (the biolo"ist) ma% not be a fre+uent user of computer technolo"%
!hese software tools must be made a#ailable o#er the internet "i#en the "lobal
distribution of the scientific research communit%
!he 5BI pro#ides a wide ran"e of biolo"ical data anal%sis tools that fall into the
followin" four ma,or cate"ories:
-imilarit% -earchin" !ools
'rotein /unction 2nal%sis
-tructural 2nal%sis
-e+uence 2nal%sis
-imilarit% -earchin" !ools
.omolo"ous se+uences are se+uences that are related b% di#er"ence from a common
ancestor. !hus the de"ree of similarit% between two se+uences can be measured while
their homolo"% is a case of bein" either true of false. !his set of tools can be used to
identif% similarities between no#el +uer% se+uences of unknown structure and function
and database se+uences whose structure and function ha#e been elucidated.
'rotein /unction 2nal%sis
!his "roup of pro"rams allow %ou to compare %our protein se+uence to the secondar% (or
deri#ed) protein databases that contain information on motifs& si"natures and protein
domains. .i"hl% si"nificant hits a"ainst these different pattern databases allow %ou to
appro$imate the biochemical function of %our +uer% protein.
-tructural 2nal%sis
!his set of tools allow %ou to compare structures with the known structure databases. !he
function of a protein is more directl% a conse+uence of its structure rather than its
se+uence with structural homolo"s tendin" to share functions. !he determination of a
protein<s 20/90 structure is crucial in the stud% of its function.
-e+uence 2nal%sis
!his set of tools allows %ou to carr% out further& more detailed anal%sis on %our +uer%
se+uence includin" e#olutionar% anal%sis& identification of mutations& h%dropath%
re"ions& =p> islands and compositional biases. !he identification of these and other
biolo"ical properties are all clues that aid the search to elucidate the specific function of
%our se+uence.
*eal world applications of bioinformatics
!he science of bioinformatics has man% beneficial uses in the modern da% world.
!hese include the followin":
1. 3olecular medicine
o 1.1 3ore dru" tar"ets
o 1.2 'ersonalised medicine
o 1.9 're#entati#e medicine
o 1.? >ene therap%
2. 3icrobial "enome applications
o 2.1 (aste cleanup
o 2.2 =limate chan"e
o 2.9 2lternati#e ener"% sources
o 2.? Biotechnolo"%
o 2.5 2ntibiotic resistance
o 2.@ /orensic anal%sis of microbes
o 2.A !he realit% of bioweapon creation
o 2.B 5#olutionar% studies
9. 2"riculture
o 9.1 =rops
o 9.2 Insect resistance
o 9.9 Impro#e nutritional +ualit%
o 9.? >row crops in poorer soils and that are drou"ht resistant
?. 2nimals
5. =omparati#e studies
1. 3olecular medicine
!he human "enome will ha#e profound effects on the fields of biomedical research and
clinical medicine. 5#er% disease has a "enetic component. !his ma% be inherited (as is
the case with an estimated 9:::4?::: hereditar% disease includin" =%stic /ibrosis and
.untin"tons disease) or a result of the bod%<s response to an en#ironmental stress which
causes alterations in the "enome (e". cancers& heart disease& diabetes..).
!he completion of the human "enome means that we can search for the "enes directl%
associated with different diseases and be"in to understand the molecular basis of these
diseases more clearl%. !his new knowled"e of the molecular mechanisms of disease will
enable better treatments& cures and e#en pre#entati#e tests to be de#eloped.
!op
1.1 3ore dru" tar"ets
2t present all dru"s on the market tar"et onl% about 5:: proteins. (ith an impro#ed
understandin" of disease mechanisms and usin" computational tools to identif% and
#alidate new dru" tar"ets& more specific medicines that act on the cause& not merel% the
s%mptoms& of the disease can be de#eloped. !hese hi"hl% specific dru"s promise to ha#e
fewer side effects than man% of toda%<s medicines.
!op
1.2 'ersonalised medicine
=linical medicine will become more personalised with the de#elopment of the field of
pharmaco"enomics. !his is the stud% of how an indi#idual<s "enetic inheritence affects
the bod%<s response to dru"s. 2t present& some dru"s fail to make it to the market because
a small percenta"e of the clinical patient population show ad#erse affects to a dru" due to
se+uence #ariants in their 012.
2s a result& potentiall% life sa#in" dru"s ne#er make it to the marketplace. !oda%& doctors
ha#e to use trial and error to find the best dru" to treat a particular patient as those with
the same clinical s%mptoms can show a wide ran"e of responses to the same treatment. In
the future& doctors will be able to anal%se a patient<s "enetic profile and prescribe the best
a#ailable dru" therap% and dosa"e from the be"innin".
!he followin" article contains more information:
pharmaco"enomics
!op
1.9 're#entati#e medicine
(ith the specific details of the "enetic mechanisms of diseases bein" unra#elled& the
de#elopment of dia"nostic tests to measure a persons susceptibilit% to different diseases
ma% become a distinct realit%. 're#entati#e actions such as chan"e of lifest%le or ha#in"
treatment at the earliest possible sta"es when the% are more likel% to be successful& could
result in hu"e ad#ances in our stru""le to con+uer disease.
!he followin" article contains more information:
"ene testin"
!op
1.? >ene therap%
In the not too distant future& the potential for usin" "enes themsel#es to treat disease ma%
become a realit%. >ene therap% is the approach used to treat& cure or e#en pre#ent disease
b% chan"in" the e$pression of a persons "enes. =urrentl%& this field is in its infantile sta"e
with clinical trials for man% different t%pes of cancer and other diseases on"oin".
!he followin" articles contain more information:
"ene therap% present/future
fundamentals of "ene therap%
"ene therap% clinical trials
+uestion/answers about "ene therap%
"ene therap% in the %ear 2:2:
"ene therap% research re+uirements
2. 3icrobial "enome applications
3icroor"anisms are ubi+uitous& that is the% are found e#er%where. !he% ha#e been found
sur#i#in" and thri#in" in e$tremes of heat& cold& radiation& salt& acidit% and pressure. !he%
are present in the en#ironment& our bodies& the air& food and water.
!raditionall%& use has been made of a #ariet% of microbial properties in the bakin"&
brewin" and food industries. !he arri#al of the complete "enome se+uences and their
potential to pro#ide a "reater insi"ht into the microbial world and its capacities could
ha#e broad and far reachin" implications for en#ironment& health& ener"% and industrial
applications. /or these reasons& in 1CC?& the 7- 0epartment of 5ner"% (0;5) initiated
the 3>' (3icrobial >enome 'ro,ect) to se+uence "enomes of bacteria useful in ener"%
production& en#ironmental cleanup& industrial processin" and to$ic waste reduction.
B% stud%in" the "enetic material of these or"anisms& scientists can be"in to understand
these microbes at a #er% fundamental le#el and isolate the "enes that "i#e them their
uni+ue abilities to sur#i#e under e$treme conditions.
!op
2.1 (aste cleanup
0einococcus radiodurans is known as the world<s tou"hest bacteria and it is the most
radiation resistant or"anism known. -cientists are interested in this or"anism because of
its potential usefulness in cleanin" up waste sites that contain radiation and to$ic
chemicals.
!he followin" articles contain more information:
superbu" 4 cleans up uranium from to$ic waste sites
3icrobial >enome 'ro"ram (3>') scientists are determinin" the 012 se+uence of the
"enome of =. crescentus& one of the or"anisms responsible for sewa"e treatment.
!op
2.2 =limate chan"e
Increasin" le#els of carbon dio$ide emission& mainl% throu"h the e$pandin" use of fossil
fuels for ener"%& are thou"ht to contribute to "lobal climate chan"e. *ecentl%& the 0;5
(0epartment of 5ner"%& 7-2) launched a pro"ram to decrease atmospheric carbon
dio$ide le#els. ;ne method of doin" so is to stud% the "enomes of microbes that use
carbon dio$ide as their sole carbon source.
!he followin" articles contain more information:
microbes and climate chan"e
!op
2.9 2lternati#e ener"% sources
-cientists are stud%in" the "enome of the microbe =hlorobium tepidum which has an
unusual capacit% for "eneratin" ener"% from li"ht.
!op
2.? Biotechnolo"%
!he archaeon 2rchaeo"lobus ful"idus and the bacterium !hermoto"a maritima ha#e
potential for practical applications in industr% and "o#ernment4funded en#ironmental
remediation. !hese microor"anisms thri#e in water temperatures abo#e the boilin" point
and therefore ma% pro#ide the 0;5& the 0epartment of 0efence& and pri#ate companies
with heat4stable enD%mes suitable for use in industrial processes.
;ther industriall% useful microbes include& =or%nebacterium "lutamicum which is of
hi"h industrial interest as a research ob,ect because it is used b% the chemical industr% for
the biotechnolo"ical production of the amino acid l%sine. !he substance is emplo%ed as a
source of protein in animal nutrition. 6%sine is one of the essential amino acids in animal
nutrition. Biotechnolo"icall% produced l%sine is added to feed concentrates as a source of
protein& and is an alternati#e to so%beans or meat and bonemeal.
Eanthomonas campestris p#. is "rown commerciall% to produce the e$opol%saccharide
$anthan "um& which is used as a #iscosif%in" and stabilisin" a"ent in man% industries.
6actococcus lactis is one of the most important micro4or"anisms in#ol#ed in the dair%
industr%& it is a non4patho"enic rod4shaped bacterium that is critical for manufacturin"
dair% products like buttermilk& %o"urt and cheese. !his bacterium& 6actococcus lactis
ssp.& is also used to prepare pickled #e"etables& beer& wine& some breads and sausa"es and
other fermented foods. *esearchers anticipate that understandin" the ph%siolo"% and
"enetic make4up of this bacterium will pro#e in#aluable for food manufacturers as well
as the pharmaceutical industr%& which is e$plorin" the capacit% of 6. lactis to ser#e as a
#ehicle for deli#erin" dru"s.
!op
2.5 2ntibiotic resistance
-cientists ha#e been e$aminin" the "enome of 5nterococcus faecalis a leadin" cause of
bacterial infection amon" hospital patients. !he% ha#e disco#ered a #irulence re"ion
made up of a number of antibiotic4resistant "enes that ma% contribute to the bacterium<s
transformation from a harmless "ut bacteria to a menacin" in#ader. !he disco#er% of the
re"ion& known as a patho"enicit% island& could pro#ide useful markers for detectin"
patho"enic strains and help to establish controls to pre#ent the spread of infection in
wards.
!he followin" articles contain more information:
3*-2 superbu"
rise of antibiotic resistance
disco#er% of no#el antibiotics
!op
2.@ /orensic anal%sis of microbes
-cientists used their "enomic tools to help distin"uish between the strain of Bacillus
anthracis that was used in the summer of 2::1 terrorist attack in /lorida with that of
closel% related anthra$ strains.
!op
2.A !he realit% of bioweapon creation
-cientists ha#e recentl% built the #irus poliom%elitis usin" entirel% artificial means. !he%
did this usin" "enomic data a#ailable on the Internet and materials from a mail4order
chemical suppl%. !he research was financed b% the 7- 0epartment of 0efence as part of
a biowarfare response pro"ram to pro#e to the world the realit% of bioweapons. !he
researchers also hope their work will discoura"e officials from e#er rela$in" pro"rams of
immunisation. !his pro,ect has been met with #er% mi$ed feeelin"s& more...
!op
2.B 5#olutionar% studies
!he se+uencin" of "enomes from all three domains of life& eukar%ota& bacteria and
archaea means that e#olutionar% studies can be performed in a +uest to determine the tree
of life and the last uni#ersal common ancestor.
/or more interestin" stories& check the archi#e at the >enome 1ews 1etwork (>11).
/or information on structural& functional and comparati#e anal%sis of "enomes and "enes
from a wide #ariet% of or"anisms see !he Institute of >enomic *esearch (!I>*).
!op
9. 2"riculture
!he se+uencin" of the "enomes of plants and animals should ha#e enormous benefits for
the a"ricultural communit%. Bioinformatic tools can be used to search for the "enes
within these "enomes and to elucidate their functions. !his specific "enetic knowled"e
could then be used to produce stron"er& more drou"ht& disease and insect resistant crops
and impro#e the +ualit% of li#estock makin" them healthier& more disease resistant and
more producti#e.
!op
9.1 =rops
=omparati#e "enetics of the plant "enomes has shown that the or"anisation of their "enes
has remained more conser#ed o#er e#olutionar% time than was pre#iousl% belie#ed.
!hese findin"s su""est that information obtained from the model crop s%stems can be
used to su""est impro#ements to other food crops. 2rabidopsis thaliana (water cress) and
;r%Da sati#a (rice) are e$amples of a#ailable complete plant "enomes.
!op
9.2 Insect resistance
>enes from Bacillus thurin"iensis that can control a number of serious pests ha#e been
successfull% transferred to cotton& maiDe and potatoes. !his new abilit% of the plants to
resist insect attack means that the amount of insecticides bein" used can be reduced and
hence the nutritional +ualit% of the crops is increased.
!op
9.9 Impro#e nutritional +ualit%
-cientists ha#e recentl% succeeded in transferrin" "enes into rice to increase le#els of
Fitamin 2& iron and other micronutrients. !his work could ha#e a profound impact in
reducin" occurrences of blindness and anaemia caused b% deficiencies in Fitamin 2 and
iron respecti#el%.
-cientists ha#e inserted a "ene from %east into the tomato& and the result is a plant whose
fruit sta%s lon"er on the #ine and has an e$tended shelf life& more...
!op
9.? >row in poorer soils and drou"ht resistant
'ro"ress has been made in de#elopin" cereal #arieties that ha#e a "reater tolerance for
soil alkalinit%& free aluminium and iron to$icities. !hese #arieties will allow a"riculture to
succeed in poorer soil areas& thus addin" more land to the "lobal production base.
*esearch is also in pro"ress to produce crop #arieties capable of toleratin" reduced water
conditions.
!op
?. 2nimals
-e+uencin" pro,ects of man% farm animals includin" cows& pi"s and sheep are now well
under wa% in the hope that a better understandin" of the biolo"% of these or"anisms will
ha#e hu"e impacts for impro#in" the production and health of li#estock and ultimatel%
ha#e benefits for human nutrition.
!he followin" articles contain more information:
5nsembl "enome browser
animal databases at the *oslin Institute
!op
5. =omparati#e studies
2nal%sin" and comparin" the "enetic material of different species is an important method
for stud%in" the functions of "enes& the mechanisms of inherited diseases and species
e#olution. Bioinformatics tools can be used to make comparisons between the numbers&
locations and biochemical functions of "enes in different or"anisms.
;r"anisms that are suitable for use in e$perimental research are termed model or"anisms.
!he% ha#e a number of properties that make them ideal for research purposes includin"
short life spans& rapid reproduction& bein" eas% to handle& ine$pensi#e and the% can be
manipulated at the "enetic le#el.
2n e$ample of a human model or"anism is the mouse. 3ouse and human are #er%
closel% related (CBG) and for the most part we see a one to one correspondence between
"enes in the two species. 3anipulation of the mouse at the molecular le#el and "enome
comparisons between the two species can and is re#ealin" detailed information on the
functions of human "enes& the e#olutionar% relationship between the two species and the
molecular mechanisms of man% human diseases.
!he followin" articles contain more information:
functional and comparati#e "enomics fact sheet 4 wh% use mouse)
what is a model or"anism)
model or"anisms for biomedical research
!op
In this ne$t section ne$t we will look at a basic introduction to molecular biolo"%