biological integrated knowledge environment
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Biological Integrated Knowledge Environment. - PowerPoint PPT PresentationTRANSCRIPT
Biological Integrated Knowledge Environment
This demonstration is best viewed as a slide show.To do this, click Slide Show on the top tool bar, then View show.
What follows is an illustration of how BioBIKE can solve interesting scientific problems that would be very difficult for the nonprogramming biologist to approach in any other way. The example uses BioBIKE's graphical programming language, which is under development. However, every operation is already possible using the text-base language, which you can access from http::/ramsites.net/~biobike
Click to move on to the next slide.
What Defines Cyanobacteria?
Cyanobacteria comprise an ancient and coherent group of organisms that happen to look alike (at least to our eyes). In fact, the genetic diversity of cyanobacteria greatly exceeds that of vertebrates, a group we consider as consisting of very different creatures. Amidst the difference, what makes cyanobacteria cyanobacteria?
What Defines Cyanobacteria?
Another way to put this question is:What genes are in common amongstall cyanobacteria?
By analyzing the functions of these genes, we may deduce the characteristics that unite cyanobacteria.
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We'll use BioBIKE to accomplish the following tasks: - Define a set of protein common to all cyanobacteria - Examine this set to discern core cyanobacterial functionsThe first set is to define a set, so click the Definition button in the Pallete.
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APPLY-FUNCTION – Applies a function to a list of values
ASSIGN – Sets a variable to a given value
DEFINE – Sets for the first time a variable to a given value
DEFINE-FUNCTION – Defines operation of a new function MY-FUNCTIONS – Lists functions you have defind MY-VARIABLES – Lists variables you have defined SWAP – Gives x's value to y and y's value to x
Clicking Definition brings up a menu related to defining sets, variables, and functions.Click the green triangle next to Define (Clicking Define itself would bring up a description of the function).
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DEFINE ASvariable name value
A function box appears, with internal boxes telling you what the function needs. Click on the first entry box to provide the name of the set you're defining.
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DEFINE AScore-proteins value
The box becomes selected (outlined in red). Type in the box the name of the set (or for now, just click).Then click on the value box, where you'll provide the definition of the set.
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DEFINE AScore-proteins value
You want to define this set as all protein common to all cyanobacterial genomes. Click the Genomes button in the Pallette to bring up functions that work on genomes.
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DEFINE
Auto
AScore-proteins
CHROMOSOME-OF - Returns chromosome' s frame
CODING-GENES-OF - Returns those genes that encode proteins
COMMON-ORTHOLOGS-OF - Returns orthologs common to all organisms in the given list
DOWNSTREAM-SEQUENCES-OF - Undocumented
GENES-OF - Returns the gene of given organism, replicon, gene, protein
INTERGENIC-SEQUENCES-OF - Returns sequences between genes of an organism
NICKNAMES-OF - Returns nicknames of given organism
NONCODING-GENES-OF - Returns those genes that do not encode proteins
ORGANISM-OF - Returns organism's frame
PROTEINS-OF - Returns proteins' frames REPLICON-OF - Returns chromosome, replicon (plasmid) or contig's frame
SEQUENCE-OF - Returns the sequence of the given gene, protein, contig, replicon, or genome UPSTREAM-SEQUENCES-OF - Returns sequences upstream of a set of genes
COMMON-ORTHOLOGS-OF sounds promising ("orthologs" are, in brief, those proteins related by common evolutionary descent). You could find out more by clicking on the function, but for now, click on the triangle next to the function.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF set of organisms
all-cyanobacteriafilamentous-cyanobacteria
heterocystous-cyanobacteriamarine-cyanobacteria
unicellular-cyanobacteria
The function fills the definition hole and, as before, tells you what it needs to know in order to function. Click on the green down arrow to see appropriate choices. Common orthologs amongst all-cyanobacteria is what you want, so click on that.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
The definition seems to be complete, so click the rightward green GO triangle next to define to accomplish the task.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
The result appears in the Results window below. Evidently there are 744 proteins in common amongst cyanobacteria (they're listed in terms of the protein of Anabaena PCC 7120). But what are they? To find the descrip-tions of these proteins click the Genes/Proteins button in the Pallette.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
Description-analysis – Properties of genes and proteins
Gene-Neighborhood – Genes/sequences around a given gene or coordinate
Translation – Codon amino acid conversions and properties of amino acids
Gene-protein-types – Type checks related to genes and proteins
You're given four categories of choices. Description-analysis looks like the most likely choice, so click the green GO triangle next to that.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
Description-analysis – Properties of genes and proteins
Gene-Neighborhood – Genes/sequences around a given gene or coordinate
Translation – Codon amino acid conversions and properties of amino acids
Gene-protein-types – Type checks related to genes and proteins
COG-ID-OF - Returns the COG ID of given gene or protein
DESCRIPTION-OF - Returns best description of given gene[s] or protein[s]
GENE-DESCRIBED-BY - Returns gene annotated as given
GENE-NAMED - Converts string name into gene frame
GENE-OF - Returns the gene of given organism, replicon, gene, protein
HYDROPHOBICITY-OF - Returns hydrophobicity score for amino acids
LENGTH-OF - Returns the length of a given entity
LENGTHS-OF - Returns the length of each entity in a list of entities
MW-OF - Calculates molecular weight of amino acid sequence
ORTHOLOG-OF – Returns phylogenetically related gene or protein
PROTEIN-OF - Returns protwib of given organism, replicon, gene, protein
SEQUENCE-OF - Returns the sequence of the given entity
Good guess! That got me to DESCRIPTION-OF, which seems very likely to do what you want. Click the green GO triangle next to that.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
DESCRIPTIONS-OF entity
The usual function box appears. You could type in the name of your set, core-proteins, but you might misspell it. Click on the downward green arrow to get appropriate choices to put in the entity box.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
DESCRIPTIONS-OF entity
(specific gene)(previous result)
core-proteins
Sets and variables you've previously defined appear as appropriate choices. Click on core-proteins.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
DESCRIPTIONS-OF core-proteins
You could execute the function now (clicking the GO triangle), but this will get you just the descriptions. You'd like them labeled with the protein name. Click on the white/green MORE arrow in the upper right corner to see what optional capabilities the function supports.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
DESCRIPTIONS-OF core-proteinsLABELED
LENGTH
Labeling is evidently one of the options. Click on LABELED.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 1: A7120.p-All0004 A7120.p-All0005 A7120.p-All0006 A7120.p-All0007 A7120.p-All0008 A7120.p-Asl0009 A7120.p-All0010 A7120.p-All0011 A7120.p-Alr0033 A7120.p-All0036 A7120.p-Alr0044 A7120.p-Alr0045 ...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
That's all you want to specify for the descriptions, so click on the right GO triangle to get the result.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
The result appears in the Result window,… at least part of it. To see the whole thing, click on RESULT 2.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
Result 2A7120.p-All0004 "ATP synthase subunit gamma" A7120.p-All0005 "ATP synthase subunit alpha" A7120.p-All0006 "ATP synthase subunit delta" A7120.p-All0007 "ATP synthase subunit b" A7120.p-All0008 "ATP synthase subunit b" A7120.p-Asl0009 "ATP synthase subunit c" A7120.p-All0010 "ATP synthase subunit a" A7120.p-All0011 "ATP synthase subunit 1" A7120.p-Alr0033 "DHNA phythltransferase" A7120.p-All0036 "UDP-N-acetylmuramoylalanyl-D-gA7120.p-Alr0044 "hypothetical protein" A7120.p-Alr0045 "hypothetical protein" A7120.p-All0049 "DNA mismatch repair protein" A7120.p-Alr0051 "IMP dehydrogenase" A7120.p-Alr0052 "thioredoxin" A7120.p-Alr0063 "ribosome binding factor A" A7120.p-All0082 "riboflavin biosynthesis proteiA7120.p-Alr0088 "single-stranded DNA-binding pr A7120.p-Alr0094 "glutamate racemase" A7120.p-Alr0096 "solanesyl diphosphate synthase A7120.p-All0109 "photosystem I subunit III precA7120.p-Alr0110 "sialoglycoprotease" A7120.p-Alr0115 "N5-glutamine methyltransferase A7120.p-Alr0116 "hypothetical protein"
You can use the scroll bar of the result window to scroll through all of the descriptions, but even with what you see right now, certain things stand out. First, many of the descriptions are of expected proteins (e.g. ATP synthase). But you see two that are surprising: "hypothetical protein" (click to continue).
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
Result 2A7120.p-All0004 "ATP synthase subunit gamma" A7120.p-All0005 "ATP synthase subunit alpha" A7120.p-All0006 "ATP synthase subunit delta" A7120.p-All0007 "ATP synthase subunit b" A7120.p-All0008 "ATP synthase subunit b" A7120.p-Asl0009 "ATP synthase subunit c" A7120.p-All0010 "ATP synthase subunit a" A7120.p-All0011 "ATP synthase subunit 1" A7120.p-Alr0033 "DHNA phythltransferase" A7120.p-All0036 "UDP-N-acetylmuramoylalanyl-D-gA7120.p-Alr0044 "hypothetical protein" A7120.p-Alr0045 "hypothetical protein" A7120.p-All0049 "DNA mismatch repair protein" A7120.p-Alr0051 "IMP dehydrogenase" A7120.p-Alr0052 "thioredoxin" A7120.p-Alr0063 "ribosome binding factor A" A7120.p-All0082 "riboflavin biosynthesis proteiA7120.p-Alr0088 "single-stranded DNA-binding pr A7120.p-Alr0094 "glutamate racemase" A7120.p-Alr0096 "solanesyl diphosphate synthase A7120.p-All0109 "photosystem I subunit III precA7120.p-Alr0110 "sialoglycoprotease" A7120.p-Alr0115 "N5-glutamine methyltransferase A7120.p-Alr0116 "hypothetical protein"
Hypothetical protein? Proteins possessed by cyanobacteria separated perhaps by over two million years of evolution must have critical functions. Seeing this result, you've decided to change course and identify all core proteins annotated "hypothetical". Perhaps we can learn the most from them. Click the white/red X to leave the Result window.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
To look for those highly conserved hypothetical proteins, you need to search for the words "hypothetical protein" in the descriptions. The descriptions are strings (collections of letters and other characters). So click on the String/Sequences button of the pallette.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
String-analysis - Functions that analyze the properties of strings
String-extraction - Functions that deliver parts of strings
String-production - Functions that manipulate and produce strings
String-type-checks - Functions that determine the type of a string
String-analysis looks good. Click on its GO triangle to find a function that might work to identify "hypothetical protein" in the descriptions.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
String-analysis - Functions that analyze the properties of strings
String-extraction - Functions that deliver parts of strings
String-production - Functions that manipulate and produce strings
String-type-checks - Functions that determine the type of a string
ALIGNMENT-OF – Aligns sequences via Clustal
ALPHABET-OF – Returns the minimal string of characters contained in string
COUNT-OF - Returns the number of times the query appears in the target
COUNTS-OF – Returns the number of times the query(s) appear in the target(s)
LENGTH-OF – Returns the length of a given entity
LENGTHS-OF – Returns the length of each entity in a list of entities
MATCH-OF – Searches target for first instance of query
MATCHES-OF – Searches target for all instances of query
MATCHES-OF seems perfect. Click on the GO triangle next to it.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF value or category
MATCHES-OF calls for something to match. Click on the down triangle to see perhaps appropriate choices.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF
NOTEACH-OFPATTERN
PATTERNSENZYME
ENZYMESPROPERTY
PROPERTIES(specific entity)(previous result)
core-proteins
value or category
The function can find various kinds of matches – patterns, restriction sites, etc. But "hypothetical protein" is not on the list. You'll have to type it in yourself. X out of the box.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF
Type "hypothetical protein" (click for this to be done automatically.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF pothetical protein”
You need to specify where to look for these words. Click on the right green MORE arrow to extend the choices of this function.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF “hypothetical protein”
IN-EACH
IN
Choose IN-EACH, because you are looking not for "hypothetical protein" in the list of results but rather for those words within each of the individual subresults.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF IN-EACH value
(specific entity)(previous result)
core-proteins
“hypothetical protein”
Click the green MENU triangle in the value box to get a list of appropriate choices. Then, choose previous result.
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 2: ((A7120.p-All0004 "ATP synthase subunit gamma") (A7120.p-All0005 "ATP synthase subunit alpha") (A7120.p-All0006 "ATP synthase subunit delta")...(744)
DESCRIPTIONS-OF LABELEDcore-proteins
MATCHES-OF
IN-EACH previous result“hypothetical protein”
That seems to describe what you want to do, so click the green GO arrow to the left of MATCHES-OF
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DEFINE AScore-proteins COMMON-ORTHOLOGS-OF all-cyanobacteria
RESULT 3: ((A7120.p-Alr0044 hypothetical protein) (A7120.p-Alr0045 hypothetical protein) (A7120.p-Alr0116 hypothetical protein) ...(196)
DESCRIPTIONS-OF LABELEDcore-proteins
The result window gives you a list of those proteins that are conserved amongst all cyanobacteria and are currently annotated as "hypothetical". You've gotten your wish and can consider each carefully to try to find clues as to their functions… later. For now click the Exit button in the pallette).
MATCHES-OF
IN-EACH previous result“hypothetical protein”
Biological Integrated Knowledge Environment
This example illustrated:
- The power of an integrated knowledge environment You didn't need to read in any data or worry about formats. It was all there for you.
- The power of a language that knows the concepts of biology You didn't need to teach the language the concept of "ortholog". This and many other biological concepts are built in.
- The power of a graphical interface You were programming a computer. It wasn't that challenging.
- The power of creative programming in solving biological problems You didn't use a premade program but examined each intermediate result as you went. This enabled you to see an unexpected and fascinating result that would have passed you by if you got only the final result.
BioBIKE may be accessed from ramsites.net/~biobike