Regular Meeting

December 22, 2008

Mark BorodovskyIvan Antonov

11/6/2008 GATech 2

Topics

1.What have been done

2.FSMark HMM implementation

3.Answers to the previous meeting questions

4.Future work

11/6/2008 GATech 3

What have been done

•HMM implementation in FSMark has been changed

•Some questions from the previous meeting have been answered

FSMark HMM implementation

11/6/2008 GATech 5

Current HMM implementation

• Currently for a given position i we look backward on 2 nucleotides instead of looking forward

• FSMark starts examining sequence from the 3rd position only (i=2), so we have complete emission string (there are strange results if we start with 1st position)

• Since FSMark starts with i=2 gene without frame shift will have state 2

11/6/2008 GATech 6

FSMark prediction depends on FS letter

• A test has been done for a sample gene inserting different letters in the middle of the gene. FSMark-GM hmm_def file was used.

FS letter FSMark prediction

A Gene overlap

C Frame shift

G Frame shift

T Frame shift

Answers to the previous meeting

questions

11/6/2008 GATech 8

Control

Genome without frame

shifts

GeneMark 417

overlaps

FSMark-GM

118 frame shifts

True Positive

0

False Positive

118

False Negative

0

11/6/2008 GATech 9

Experiment

Genome with frame shifts in

400 genes

GeneMark 599

overlaps

FSMark-GM

325 frame shifts

True Positive

113

False Positive

212

False Negative

287

171 overlaps

caused by frame shift

11/6/2008 GATech 10

Questions to answer

• Take a look at the distribution of overlap lengths in GeneMark output

• Understand why GeneMark predicts gene overlap for less than 50% of genes with Frame Shifts. There are two possible reasons:– Missing short part, i.e. GeneMark predicts one gene only– GeneMark predicts two genes but they don’t overlap

• Try to understand why did we get more False Positive in experiment than in control

11/6/2008 GATech 11

All overlaps length (genome without FS)

0

50

100

150

200

250

300

4 7 8 10 11 13 14 16 17 19 20 22 23 25 26 29 31 32 35 38 40 43 56

11/6/2008 GATech 12

Overlaps caused by frame shift

0

5

10

15

20

25

8 11 14 17 20 23 26 29 32 35 38 41 44 47 50 53 56 59 62 65 68 71 77 89 95 140

11/6/2008 GATech 13

GeneMark analysis

• Why does GeneMark barely predict overlaps for genes with frame shift?

• In my GeneMark output there are 357 typical genes (out of 400).

• Probably I use wrong GeneMark option?

11/6/2008 GATech 14

GeneMark output statistics

Genome with frame

shifts in 400 genes

4,388 gene

s

599 gene

overlaps

335 genes with fs

171 overlaps

caused by fs

22 genes with fs

are missing

fs in 164 genes didn’t

cause overlap

4 fs caused new gene downstream the initial

gene

163 decreased

their lengths

11/6/2008 GATech 15

Conclusions

• I need to check how to run GeneMark in order to get the same 400 typical genes

• It seems that the small chunk in the shifted frame is not enough for GeneMark to predict a new gene

11/6/2008 GATech 16

Time Table

Date TODO

Dec 24, Wed

Insensitive zone length analysis for FSMark to determine length of zones 1 and 3

2009 Apply FSMark-GM to 3 typical genomes using found zone 1 and 3 lengths