Convert all the content to Literal Programming

This commit is contained in:
coolneng 2019-12-09 13:35:28 +01:00
parent fe23029144
commit 6b04676fbb
Signed by: coolneng
GPG Key ID: 9893DA236405AF57
12 changed files with 253 additions and 207 deletions

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@ -1,14 +0,0 @@
def ApproximatePatternCount(Pattern, Text, d):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern or HammingDistance(Text[i:i+len(Pattern)], Pattern) <= d:
count += 1
return count
def HammingDistance(p, q):
count = 0
for i in range(0, len(p)):
if p[i] != q[i]:
count += 1
return count

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@ -1,16 +0,0 @@
def ApproximatePatternMatching(Text, Pattern, d):
positions = []
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
positions.append(i)
elif HammingDistance(Text[i:i+len(Pattern)], Pattern) <= d:
positions.append(i)
return positions
def HammingDistance(p, q):
count = 0
for i in range(0, len(p)):
if p[i] != q[i]:
count += 1
return count

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@ -1,20 +0,0 @@
def FasterSymbolArray(Genome, symbol):
array = {}
n = len(Genome)
ExtendedGenome = Genome + Genome[0:n//2]
array[0] = PatternCount(symbol, Genome[0:n//2])
for i in range(1, n):
array[i] = array[i-1]
if ExtendedGenome[i-1] == symbol:
array[i] = array[i]-1
if ExtendedGenome[i+(n//2)-1] == symbol:
array[i] = array[i]+1
return array
def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count

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@ -1,20 +0,0 @@
def FrequentWords(Text, k):
words = []
freq = FrequencyMap(Text, k)
m = max(freq.values())
for key in freq:
if freq[key] == m:
words.append(key)
return words
def FrequencyMap(Text, k):
freq = {}
n = len(Text)
for i in range(n - k + 1):
Pattern = Text[i:i + k]
freq[Pattern] = 0
for i in range(n - k + 1):
Pattern = Text[i:i + k]
freq[Pattern] += 1
return freq

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@ -1,6 +0,0 @@
def HammingDistance(p, q):
count = 0
for i in range(0, len(p)):
if p[i] != q[i]:
count += 1
return count

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@ -1,18 +0,0 @@
def MinimumSkew(Genome):
positions = []
skew = SkewArray(Genome)
minimum = min(skew)
return [i for i in range(0, len(Genome)) if skew[i] == minimum]
def SkewArray(Genome):
Skew = []
Skew.append(0)
for i in range(0, len(Genome)):
if Genome[i] == "G":
Skew.append(Skew[i] + 1)
elif Genome[i] == "C":
Skew.append(Skew[i] - 1)
else:
Skew.append(Skew[i])
return Skew

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@ -1,6 +0,0 @@
def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count

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@ -1,6 +0,0 @@
def PatternMatching(Pattern, Genome):
positions = []
for i in range(len(Genome)-len(Pattern)+1):
if Genome[i:i+len(Pattern)] == Pattern:
positions.append(i)
return positions

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@ -1,17 +0,0 @@
def ReverseComplement(Pattern):
Pattern = Reverse(Pattern)
Pattern = Complement(Pattern)
return Pattern
def Reverse(Pattern):
reversed = Pattern[::-1]
return reversed
def Complement(Pattern):
compl = ""
complement_letters = {"A": "T", "T": "A", "C": "G", "G": "C"}
for char in Pattern:
compl += complement_letters[char]
return compl

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@ -1,11 +0,0 @@
def SkewArray(Genome):
Skew = []
Skew.append(0)
for i in range(0, len(Genome)):
if Genome[i] == "G":
Skew.append(Skew[i] + 1)
elif Genome[i] == "C":
Skew.append(Skew[i] - 1)
else:
Skew.append(Skew[i])
return Skew

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@ -1,15 +0,0 @@
def SymbolArray(Genome, symbol):
array = {}
n = len(Genome)
ExtendedGenome = Genome + Genome[0:n//2]
for i in range(n):
array[i] = PatternCount(ExtendedGenome[i:i+(n//2)], symbol)
return array
def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count

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@ -6,41 +6,114 @@
**** Origin of replication (ori) **** Origin of replication (ori)
Locating an ori is key for gene therapy (e.g. viral vectors), to introduce a theraupetic gene. Locating an ori is key for gene therapy (e.g. viral vectors), to introduce a theraupetic gene.
**** Computational approaches to find ori in Vibrio Cholerae **** Computational approaches to find ori in Vibrio Cholerae
***** Exercise: find Pattern ***** Exercise: find Pattern
We'll look for the *DnaA box* sequence, using a sliding window, in that case we will use the function [[./Code/PatternCount.py][PatternCount]] to find out how many times We'll look for the *DnaA box* sequence, using a sliding window, in that case we will use this function to find out how many times
does a sequence appear in the genome. does a sequence appear in the genome:
For the second part, we're going to calculate the frequency map of the sequences of length /k/, for that purpose we'll use [[./Code/FrequentWords.py][FrequentWords]] #+BEGIN_SRC python
def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count
#+END_SRC
For the second part, we're going to calculate the frequency map of the sequences
of length /k/, for that purpose we'll use:
#+BEGIN_SRC python
def FrequentWords(Text, k):
words = []
freq = FrequencyMap(Text, k)
m = max(freq.values())
for key in freq:
if freq[key] == m:
words.append(key)
return words
def FrequencyMap(Text, k):
freq = {}
n = len(Text)
for i in range(n - k + 1):
Pattern = Text[i:i + k]
freq[Pattern] = 0
for i in range(n - k + 1):
Pattern = Text[i:i + k]
freq[Pattern] += 1
return freq
#+END_SRC
***** Exercise: Find the reverse complement of a sequence ***** Exercise: Find the reverse complement of a sequence
We're going to generate the reverse complement of a sequence, which is the complement of a sequence, read in the same direction (5' -> 3'). We're going to generate the reverse complement of a sequence, which is the complement of a sequence, read in the same direction (5' -> 3').
In this case, we're going to use [[./Code/ReverseComplement.py][ReverseComplement]] In this case, we're going to use:
After using our function on the /Vibrio Cholerae's/ genome, we realize that some of the frequent /k-mers/ are reverse complements of other frequent ones.
#+BEGIN_SRC python
def ReverseComplement(Pattern):
Pattern = Reverse(Pattern)
Pattern = Complement(Pattern)
return Pattern
def Reverse(Pattern):
reversed = Pattern[::-1]
return reversed
def Complement(Pattern):
compl = ""
complement_letters = {"A": "T", "T": "A", "C": "G", "G": "C"}
for char in Pattern:
compl += complement_letters[char]
return compl
#+END_SRC
After using our function on the /Vibrio Cholerae's/ genome, we realize that some of the frequent /k-mers/ are reverse complements of other frequent ones.
***** Exercise: Find a subsequence within a sequence ***** Exercise: Find a subsequence within a sequence
We're going to find the ocurrences of a subsquence inside a sequence, and save the index of the first letter in the sequence. We're going to find the ocurrences of a subsquence inside a sequence, and save the index of the first letter in the sequence.
This time, we'll use [[./Code/PatternMatching.py][PatternMatching]] This time, we'll use:
After using our function on the /Vibrio Cholerae's/ genome, we find out that the /9-mers/ with the highest frequency appear in cluster.
This is strong statistical evidence that our subsequences are /DnaA boxes/. #+BEGIN_SRC python
def PatternMatching(Pattern, Genome):
positions = []
for i in range(len(Genome)-len(Pattern)+1):
if Genome[i:i+len(Pattern)] == Pattern:
positions.append(i)
return positions
#+END_SRC
After using our function on the /Vibrio Cholerae's/ genome, we find out that the /9-mers/ with the highest frequency appear in cluster.
This is strong statistical evidence that our subsequences are /DnaA boxes/.
**** Computational approaches to find ori in any bacteria **** Computational approaches to find ori in any bacteria
Now that we're pretty confident about the /DnaA boxes/ sequences that we found, we are going to check if they are a common pattern in the rest of bacterias. Now that we're pretty confident about the /DnaA boxes/ sequences that we found, we are going to check if they are a common pattern in the rest of bacterias.
We're going to find the ocurrences of the sequences in /Thermotoga petrophila/ using [[./Code/PatternCount.py][PatternCount]] We're going to find the ocurrences of the sequences in /Thermotoga petrophila/
with:
After the execution, we observe that there are *no* ocurrences of the sequences found in /Vibrio Cholerae/. #+BEGIN_SRC python
We can conclude that different bacterias have different /DnaA boxes/. def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count
#+END_SRC
We have to try another computational approach then, find clusters of /k-mers/ repeated in a small interval. After the execution, we observe that there are *no* ocurrences of the sequences found in /Vibrio Cholerae/.
We can conclude that different bacterias have different /DnaA boxes/.
We have to try another computational approach then, find clusters of /k-mers/ repeated in a small interval.
** Week 2 ** Week 2
@ -48,70 +121,193 @@
**** Replication process **** Replication process
The /DNA polymerases/ start replicating while the parent strands are unraveling. The /DNA polymerases/ start replicating while the parent strands are unraveling.
On the lagging strand, the DNA polymerase waits until the replication fork opens around 2000 nucleotides, and because of that it forms Okazaki fragments. On the lagging strand, the DNA polymerase waits until the replication fork opens around 2000 nucleotides, and because of that it forms Okazaki fragments.
We need 1 primer for the leading strand and 1 primer per Okazaki fragment for the lagging strand. We need 1 primer for the leading strand and 1 primer per Okazaki fragment for the lagging strand.
While the Okazaki fragments are being synthetized, a /DNA ligase/ starts joining the fragments together. While the Okazaki fragments are being synthetized, a /DNA ligase/ starts joining the fragments together.
**** Computational approach to find ori using deamination **** Computational approach to find ori using deamination
As the lagging strand is always waiting for the helicase to go forward, the lagging strand is mostly in single-stranded configuration, which is more prone to mutations. As the lagging strand is always waiting for the helicase to go forward, the lagging strand is mostly in single-stranded configuration, which is more prone to mutations.
One frequent form of mutation is *deamination*, a process that causes cytosine to convert into thymine. This means that cytosine is more frequent in half of the genome. One frequent form of mutation is *deamination*, a process that causes cytosine to convert into thymine. This means that cytosine is more frequent in half of the genome.
***** Exercise: count the ocurrences of cytosine ***** Exercise: count the ocurrences of cytosine
We're going to count the ocurrences of the bases in a genome and include them in a symbol array, for that purpose we'll use [[./Code/SymbolArray.py][SymbolArray]] We're going to count the ocurrences of the bases in a genome and include them in
After executing the program, we realize that the algorithm is too inefficient. a symbol array, for that purpose we'll use:
#+BEGIN_SRC python
def SymbolArray(Genome, symbol):
array = {}
n = len(Genome)
ExtendedGenome = Genome + Genome[0:n//2]
for i in range(n):
array[i] = PatternCount(ExtendedGenome[i:i+(n//2)], symbol)
return array
def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count
#+END_SRC
After executing the program, we realize that the algorithm is too inefficient.
***** Exercise: find a better algorithm for the previous exercise ***** Exercise: find a better algorithm for the previous exercise
This time, we are going to evaluate an element /i+1/, using the element /i/. We'll use [[./Code/FasterSymbolArray.py][FasterSymbolArray]] to achieve this This time, we are going to evaluate an element /i+1/, using the element /i/.
After executing the program we see that it's a viable algorithm, with a complexity of /O(n)/ instead of the previous /O(n²)/. We'll use the following algorithm:
In /Escherichia Coli/ we plotted the result of our program:
#+CAPTION: Symbol array for Cytosine in E. Coli Genome] #+BEGIN_SRC python
[[./Assets/e-coli.png]] def FasterSymbolArray(Genome, symbol):
array = {}
n = len(Genome)
ExtendedGenome = Genome + Genome[0:n//2]
array[0] = PatternCount(symbol, Genome[0:n//2])
for i in range(1, n):
array[i] = array[i-1]
if ExtendedGenome[i-1] == symbol:
array[i] = array[i]-1
if ExtendedGenome[i+(n//2)-1] == symbol:
array[i] = array[i]+1
return array
From that graph, we conclude that ori is located around position 4000000, because that's where the Cytosine concentration is the lowest,
which indicates that the region stays single-stranded for the longest time. def PatternCount(Text, Pattern):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
count = count+1
return count
#+END_SRC
After executing the program we see that it's a viable algorithm, with a complexity of /O(n)/ instead of the previous /O(n²)/.
In /Escherichia Coli/ we plotted the result of our program:
#+CAPTION: Symbol array for Cytosine in E. Coli Genome]
[[./Assets/e-coli.png]]
From that graph, we conclude that ori is located around position 4000000, because that's where the Cytosine concentration is the lowest,
which indicates that the region stays single-stranded for the longest time.
**** The Skew Diagram **** The Skew Diagram
Usually scientists measure the difference between /G - C/, which is *higher on the lagging strand* and *lower on the leading strand*. Usually scientists measure the difference between /G - C/, which is *higher on the lagging strand* and *lower on the leading strand*.
***** Exercise: Synthetize a Skew Array ***** Exercise: Synthetize a Skew Array
We're going to make a Skew Diagram, for that we'll first need a Skew Array. For that purpose we wrote [[./Code/SkewArray.py][SkewArray]] We're going to make a Skew Diagram, for that we'll first need a Skew Array. For
We can see the utility of a Skew Diagram looking at the one from /Escherichia Coli/: that purpose we wrote:
#+CAPTION: Symbol array for Cytosine in E. Coli Genome] #+BEGIN_SRC python
[[./Assets/skew_diagram.png]] def SkewArray(Genome):
Skew = []
Skew.append(0)
for i in range(0, len(Genome)):
if Genome[i] == "G":
Skew.append(Skew[i] + 1)
elif Genome[i] == "C":
Skew.append(Skew[i] - 1)
else:
Skew.append(Skew[i])
return Skew
#+END_SRC
Ori should be located where the skew is at its minimum value. We can see the utility of a Skew Diagram looking at the one from /Escherichia Coli/:
#+CAPTION: Symbol array for Cytosine in E. Coli Genome]
[[./Assets/skew_diagram.png]]
Ori should be located where the skew is at its minimum value.
***** Exercise: Efficient algorithm for locating ori ***** Exercise: Efficient algorithm for locating ori
Now that we know more about ori's skew value, we're going to construct a better algorithm to find it. We'll do that in [[./Code/MinimumSkew.py][MinimumSkew]] Now that we know more about ori's skew value, we're going to construct a better
algorithm to find it:
#+BEGIN_SRC python
def MinimumSkew(Genome):
positions = []
skew = SkewArray(Genome)
minimum = min(skew)
return [i for i in range(0, len(Genome)) if skew[i] == minimum]
def SkewArray(Genome):
Skew = []
Skew.append(0)
for i in range(0, len(Genome)):
if Genome[i] == "G":
Skew.append(Skew[i] + 1)
elif Genome[i] == "C":
Skew.append(Skew[i] - 1)
else:
Skew.append(Skew[i])
return Skew
#+END_SRC
**** Finding /DnaA boxes/ **** Finding /DnaA boxes/
When we look for /DnaA boxes/ in the minimal skew region, we can't find highly repeated /9-mers/ in /Escherichia Coli/. When we look for /DnaA boxes/ in the minimal skew region, we can't find highly repeated /9-mers/ in /Escherichia Coli/.
But we find approximate sequences that are similar to our /9-mers/ and only differ in 1 nucleotide. But we find approximate sequences that are similar to our /9-mers/ and only differ in 1 nucleotide.
***** Exercise: Calculate Hamming distance ***** Exercise: Calculate Hamming distance
The Hamming distance is the number of mismatches between 2 strings, we'll solve this problem in [[./Code/HammingDistance][HammingDistance]] The Hamming distance is the number of mismatches between 2 strings, we'll solve this problem in [[./Code/HammingDistance][HammingDistance]]
***** Exercise: Find approximate patterns ***** Exercise: Find approximate patterns
Now that we have our Hamming distance, we have to find the approximate sequences. We'll do this in [[./Code/ApproximatePatternMatching.py][ApproximatePatternMatching.py]] Now that we have our Hamming distance, we have to find the approximate
sequences:
#+BEGIN_SRC python
def ApproximatePatternMatching(Text, Pattern, d):
positions = []
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern:
positions.append(i)
elif HammingDistance(Text[i:i+len(Pattern)], Pattern) <= d:
positions.append(i)
return positions
def HammingDistance(p, q):
count = 0
for i in range(0, len(p)):
if p[i] != q[i]:
count += 1
return count
#+END_SRC
***** Exercise: Count the approximate patterns ***** Exercise: Count the approximate patterns
The final part is counting the approximate sequences, for that we'll use [[./Code/ApproximatePatternCount.py][ApproximatePatternCount.py]] The final part is counting the approximate sequences:
After trying out our ApproximatePatternCount in the hypothesized ori region, we find a frequent /k-mer/ with its reverse complement in /Escherichia Coli/. #+BEGIN_SRC python
We've finally found a computational method to find ori that seems correct. def ApproximatePatternCount(Pattern, Text, d):
count = 0
for i in range(len(Text)-len(Pattern)+1):
if Text[i:i+len(Pattern)] == Pattern or HammingDistance(Text[i:i+len(Pattern)], Pattern) <= d:
count += 1
return count
def HammingDistance(p, q):
count = 0
for i in range(0, len(p)):
if p[i] != q[i]:
count += 1
return count
#+END_SRC
After trying out our ApproximatePatternCount in the hypothesized ori region, we find a frequent /k-mer/ with its reverse complement in /Escherichia Coli/.
We've finally found a computational method to find ori that seems correct.
** Week 3 ** Week 3
@ -123,7 +319,6 @@ Variation in gene expression permits the cell to keep track of time.
***** Exercise: Find the most common nucleotides in each position ***** Exercise: Find the most common nucleotides in each position
We are going to create a *t x k* Motif Matrix, where *t* is the /k-mer/ string. In each position, we'll insert the most frequent nucleotide, in upper case, We are going to create a *t x k* Motif Matrix, where *t* is the /k-mer/ string. In each position, we'll insert the most frequent nucleotide, in upper case,
and the nucleotide in lower case (if there's no popular one). and the nucleotide in lower case (if there's no popular one).
Our goal is to select the *most* conserved Matrix, i.e. the Matrix with the most upper case letters. Our goal is to select the *most* conserved Matrix, i.e. the Matrix with the most upper case letters.
@ -493,5 +688,5 @@ characteristic of Greedy Algorithms, they trade optimality for speed.
** Vocabulary ** Vocabulary
- k-mer: subsquences of length /k/ in a biological sequence - k-mer: subsquences of length /k/ in a biological sequence
- Frequency map: sequence --> frequency of the sequence - Frequency map: sequence --> frequency of the sequence