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Fetrow Research Group



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The Fetrow research group has long been involved in understanding the details of molecular function of proteins. This problem is significant because of the ever-increasing numbers of protein sequences that are being determined through the genome sequencing projects. The vast majority of these proteins are of uncharacterized function; another large fraction of these proteins are mis-annotated at the molecular functional level. It is impossible, both methodologically and because of cost, to experimentally determine the function of every protein. Robust and automated computational approaches to this problem are essential.

We have developed a process, MISST (Harper, et al., 2017), to cluster proteins into functionally relevant or isofunctional groups.  The foundation of this work is a method called active site profiling (Cammer, et al. 2003).  As a proof-of-concept for functionally relevant clustering, active site profiling was applied manually to the identification of all members of each of the six subgroups of the peroxiredoxin superfamily, distinguishing all six functionally relevant groups (Prx1/AhpC, Prx6, PrxQ/BCP, Prx5, Tpx, and AhpE) that had previously been identified by experts (Nelson, et al. 2011), Even though mehods based on full sequence analysis are unable to identify each of these six groups. Active site profiling has also been applied to the cytochrome P450 family, resulting in comprehensive identification of functionally related proteins, subsequently validated experimentally (Gober, et al., 2016). 

Iterative application of this profiling process has allowed us to demonstrate functionally relevant clustering on proteins of known structure (TuLIP, Knutson et al., 2017).  Additionally, MISST was developed to apply the iterative profiling concept to protein sequences for which structure is not known.  MISST, validated on the peroxiredoxins (Harper, et al., 2017), is the first process for functionally relevant clustering that is iterative and agglomerative, both adding sequences and identifying when a group should be subdivided into functionally relevant clusters.  

MISST has been automated (Leutheauser and Fetrow, unpublished) and the automated process is being validated on a number of biologically important superfamilies, including the enolases, Radical SAMs, GSTs, beta lactamases and carbohydrate kinases.  In collaboration with Carol Parish's laboratory and student Mikaela Rosen at the University of Richmond, we are creating a comprehensive atlas of arsenate reductases and functionally related phosphatases clustered into functionally relevant groups.  

Our group also collaborate with Leslie Poole and Kim Nelson at Wake Forest University, experts in peroxiredoxin biology and biochemistry.  We have also collaborated with Eric Brustad at UNC Chapel Hill for the work on the cytochrome P450s.  Collaborators Patsy Babbitt, Tom Ferrin, and John "Scooter" Morris have been essential partners in the development of TuLIP and MISST.  The peroxiredoxin annotations identified in the 2011 Nelson paper are stored in the SFLD Database (see Akiva, et al. 2013RBVISFLD).

For more information on general research interests of our group or current projects we are involved in please visit the Research page.



Lab News and Events

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October 2016: Jacquelyn Fetrow is appointed the 15th President of her alma mater, Albright College

Jacque will soon be moving to Reading, PA, to assume the presidency of her undergraduate institution, Albright College! Spring 2017 will be focused on transitions and publications as she prepares for her next phase. Her position officially starts on June 1, 2017.

January 2017: Lab alumna Janelle Leuthaeuser Curtis gets her dream job

Janelle has been the heart and soul of the lab for years as she completed and defended her dissertation, and then as Lab Manager / Post Doctoral Research. She is now a Senior Analyst at EA Sports, based in Orlando, FL. She writes:

"I am the lead analyst for the NBA Live 18 game to be released later this year. In this role, I am responsible for answering all business questions about the game with data to back up my assertions. The questions range from the number of people purchasing and playing the game to how the players interact with the game to how we can improve acquisition and engagement in different areas of the game. Ultimately, the goal is to use data analysis to provide insights which will improve NBA Live 18 for the consumers."

We wish Janelle well and much success with a career that merges her love of data analysis with her passion for sports.

January 2017: Lab alumna Angela Harper named Churchill Scholar

Harper

Former Fetrow lab member and current Wake Forest senior Angela Harper has been named one of 15 Churchill Scholars who will study at the University of Cambridge for the academic year 2017-18. Way to go, Angela!

July 2016: Julia Hayden heads to Philadelphia

Julia photo

After working with the Fetrow Lab since summer 2013, Julia is moving on to work with City Year in the Philadelphia public schools. The Provost's Office and the lab group had an all-hands lunch to say goodbye. We will miss her!

July 2016: The Protein Society Symposium in Baltimore

Julia Hayden and Nick Biffis present posters at the 30th Annual Symposium of the Protein Society.

Julia Hayden
"Automatic clustering of the amidohydrolase superfamily"
Nick Biffis
"Automating TuLIP, a protein clustering method"

Summer 2016: URISE Scholars in the Lab

The Fetrow Group welcomes the following URISE Scholars for their pre-first-year summer research experience:

  • Destiny Pryor
  • Mikaela Rosen
  • Salmika Wairegi

January 2016: Fetrow Lab Established at the Univeristy of Richmond

With Janelle and Julia both moving to Richmond, the lab is now fully established in the Gottwald Science Center on the campus of the University of Richmond.

November 6, 2015: Dr. Janelle Leuthaeuser Successfully Defends her Dissertation!

Janelle's thesis: "Development and optimization of a clustering process that utilizes active site features to identify functionally relevant groups within protein superfamilies".

July 2015: The Protein Society Symposium in Barcelona, Spain

Janelle Leuthaeuser, Angela Harper, and Julia Hayden all presented posters at the 29th Annual Protein Society Symposium.  Angela’s poster abstract was one of three undergraduate submissions selected for oral presentation.  Julia won a Best Poster Award. Posters presented at the symposium (abstracts can be found here):

Winner, Best Poster Award: Julia Hayden
"Functional clustering of the crotonase superfamily"
Selected for oral presentation: Angela Harper
"Active site clustering identifies functional families of the peroxiredoxin superfamily"
Janelle Leuthaeuser
"Active site profile-based protein clustering is an efficient, accurate method to define protein functional groups"

July 2015: ISMB Conference in Dublin Ireland

Janelle Leuthaeuser presented a poster at the 2015 ISMB Conference entitled "Active site profile-based protein clustering is an efficient, accurate method to define protein functional groups" (abstract can be found here).

June 2015: Proteins Gordon Conference in Holderness, NH

Janelle Leuthaeuser presented a poster at the 2015 Proteins Gordon Conference: "Peroxiredoxin proteins are clustered in an efficient, functionally relevant manner using active site profile-based protein clustering."

April 2015: Julia Hayden wins Best Poster Award at Dickinson College Undergraduate Research Day

Julia presented two posters at the 30th Annual Science Student Research Symposium at Dickinson College: "Automated Functional Clustering of the Crotonase Superfamily" (best poster winner) and "The Role of Interleukin 8 During Phorbol Ester Induced Differentiation of Human Acute Myeloid Leukemia Cells" (with Prof. Michael Roberts).

March 2015: MCBIOS XII: Emerging Trends in Bioinformatics

Dr. Fetrow presents keynote speech: "What do all those proteins do? An approach to functionally relevant clustering of the protein universe"

July 2014: The Protein Society Symposium in San Diego

Janelle Leuthaeuser, Brian Westwood, Gabrielle Shea, Julia Hayden, Kiran Kumar and Angela Harper all presented posters at the 28th Annual Protein Society Symposium. Kiran's poster was selescted for oral presentation and Gabrielle won a best poster award. Posters presented at the symposium (abstracts can be found here):

Winner, Best Poster Award: Gabrielle Shea
"Utilization of an Iterative Clustering Method to group Radical SAMs in Functionally Relevant Ways "
Selected for oral presentation: Kiran Kumar
"Multi-level Iterative Functional Clustering of Glutathione Transferase Superfamily"
Angela Harper
"Active site profile-based clustering of the peroxiredoxin superfamily"
Julia Hayden
"Automated Functional Clustering of the Crotonase Superfamily based on active site motif sequences"
Janelle Leuthaeuser
"Active site profile-based clustering of enolase structures and sequences"
Brian Westwood
"Broad Scope and Coverage of Functionally Relevant Groups for Sequences in the Enolase Superfamily"

July 2014: ISMB Conference in Boston

Janelle Leuthaeuser presented a poster at the 2014 ISMB meeting entitled "Active site profile-based clustering of Enolase structures and sequences". Based on her abstract submission, she was invited to give an oral presentation at the Protein Function Special Interest Group Meeting the day before the main conference. Janelle won the Best Oral Presentation Award for her talk (abstract can be found here).