Predicting the Functional Effects of Human Short Variations Using Hidden Markov Models

With the development of sequencing technologies, more and more sequence variants are available for investigation. Different types of variants in the human genome have been identified, including single nucleotide polymorphisms (SNPs), short insertions and deletions (indels), and large structural variations such as large duplications and deletions. Of great research interest is the functional effects of these variants. Although many programs have been developed to predict the effect of SNPs, few can be used to predict the effect of indels or multiple variants, such as multiple SNPs, multiple indels, or a combination of both. Moreover, fine grained prediction of the functional outcome of variants is not available. To address these limitations, we developed a prediction framework, HMMvar, to predict the functional effects of coding variants (SNPs or indels), using profile hidden Markov models (HMMs). Based on HMMvar, we proposed HMMvar-multi to explore the joint effects of multiple variants in the same gene. For fine grained functional outcome prediction, we developed HMMvar-func to computationally define and predict four types of functional outcome of a variant: gain, loss, switch, and conservation of function.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Computer Science and Applications

Department dc:contributor.department

Computer Science

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2015

Author dc:creator

• Liu, Mingming

Chair dc:contributor.committeechair

• Zhang, Liqing

Committee members dc:contributor.committeemember

• Heath, Lenwood S.
• Wu, Xiaowei
• Hu, Jianjun
• Watson, Layne T.

• Genetic variation
• Indel
• SNP
• Hidden Markov Model

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:5906

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/73703