# Björn Dierkes, Julia Gruebner: FBN1 Bioinformatics/Sequence Analysis for Master Biotechnology

## **Exercise 1 - Pubmed**

### *1.* *How many papers are published per year?*
> * 2020 1.625.383

>Source: PubMed

### *2. How many journals are there?*

32.000

### *3. How dose Pubmed deal with first name and surname?*

Enter the author’s last name and initials without punctuation in the search box, and click Search.

If you only know the author’s last name, use the author search field tag [au], e.g., brody[au].

Names entered using either the lastname+initials format (e.g., smith ja) or the full name format (john a smith) and no search tag are searched as authors as well as collaborators, if they exist in PubMed.

Enter a full author name in natural or inverted order, e.g., julia s wong or wong julia s.

Prior to 2002, full author names were not included on PubMed citations, so full author name searches will only retrieve citations from 2002 forward, when the full author name was published in the article.
A comma following the last name for searching is optional. For some names, however, it is necessary to distinguish which name is the last name by using the comma following the last name, e.g., james, ryan.
Omit periods after initials and put all suffixes at the end, e.g., vollmer charles jr

Initials and suffixes are not required. If you include a middle initial or suffix, you will only retrieve citations for articles that were published using the middle initial or suffix.

| Gene name | Alternative gene names | Protein name | Alternative protein names
| -------- | -------- | -------- | ---
| Fibrillin-1 | ACMICD, ECTOL1, MFLS, ... | Fibrillin-1 und Asprosin | FBN

### *4. What can be found under "Advanced"?* *Which search fields are available here? How do you combine the search terms?*

More information about author searching:

To search by author using the search builder, click Advanced search and then select Author from the All Fields menu. The author search box includes an autocomplete feature.
You may click an author link on the abstract display to execute a search for the author in PubMed. Results will display using a ranking algorithm if the author name is computationally similar for additional PubMed citations.
If an author name includes only stopwords, use the author search field tag [au] to search in combination with other terms, e.g., just by[au] seizure.
Author names are automatically truncated to account for varying initials and designations such as Jr. To turn off the truncation, use double quotes around the author's name with the author search field tag [au], e.g., "smith j"[au].
Use the search field tag [1au] to search for the first personal author or [lastau] to search for the last personal author name in a citation.
For additional information on author names in PubMed, please see the journal article, "Author Name Disambiguation for PubMed."

## **Exercise 2 - Your database**

## **Exercise 3 - Research your Gene/Protein**

FBN1

### *2. Which author has been working with the protein for a long time and is perhaps a luminary/authority?*

Fibrillin (FBN1) mutations in Marfan syndrome.
Hayward C, Keston M, Brock DJ, Dietz HC.
Hum Mutat. 1992;1(1):79. doi: 10.1002/humu.1380010115.
PMID: 1301195 No abstract available.

### *3. Are there reviews of your protein in review articles?*

### *4. How do you find out whether a journal is considered "good" or "obscure"?*

### *5. Find out if there are articles about your protein in "Nature", "Cell", "Science", "eLIFE", "Nature Cell Biology", "Current Biology".*

There are some, but not that many

### *6. Which paper on your protein/gene do you have the most references and is it an important paper in the field?*
Sakai, et al. did describe the protein for the first time (1986 und 1991)

### *7. Compare your results with an alternative literature search database (EuropePMC). Can you find the results again? What is the biggest difference?*

## Exercise 4 - Introduction to FBN1

### General

### Structure

Chain: A
Length: 74 amino acids
Theoretical weight: 8,02 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
Canonical: Protein Data Bank in Europe - Knowledge Base P35555 (Residues: 2052-2125; Coverage: 3%)
Gene names: FBN, FBN1
FASTA Sequence>pdb|1apj|A
SAQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCALKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSA

Source: EMBL-EBI

### Function

Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:1860873, PubMed:15062093).

Fibrillin-1-containing microfibrils provide long-term force bearing structural support (PubMed:27026396).

In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin (PubMed:27026396).

In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus where they provide tensile strength and have anchoring roles (PubMed:27026396).

Fibrillin-1 also plays a key role in tissue homeostasis through specific interactions with growth factors, such as the bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and latent transforming growth factor-beta-binding proteins (LTBPs), cell-surface integrins and other extracellular matrix protein and proteoglycan components (PubMed:27026396).

Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (By similarity).

Negatively regulates osteoclastogenesis by binding and sequestering an osteoclast differentiation and activation factor TNFSF11 (PubMed:24039232).

This leads to disruption of TNFSF11-induced Ca2+ signaling and impairment of TNFSF11-mediated nuclear translocation and activation of transcription factor NFATC1 which regulates genes important for osteoclast differentiation and function (PubMed:24039232).

Mediates cell adhesion via its binding to cell surface receptors integrins ITGAV:ITGB3 and ITGA5:ITGB1 (PubMed:12807887, PubMed:17158881).

Binds heparin and this interaction has an important role in the assembly of microfibrils (PubMed:11461921).

Source: UniProt

### Role in diseases

Marfan syndrome (MFS)45 Publications
The disease is caused by variants affecting the gene represented in this entry. The majority of the more than a thousand mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.
Disease descriptionA hereditary disorder of connective tissue that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with Marfan syndrome, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in most of the patients and is almost always bilateral. The leading cause of premature death is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. Neonatal Marfan syndrome is the most severe form resulting in death from cardiorespiratory failure in the first few years of life.

Source: Uniprot

### Write a report:

Summarize your results in writing by preparing a draft introduction to your protein/gene. Note: You are also welcome to make an overview figure of the gene/protein function (and possible dysfunction in diseases).
If there are 2500 articles on your article, try to focus on one aspect, for example in disease xy, or in embryonic development, or in vitro biochemistry. (combine such terms in your pubmed search with AND!)

Introduction:

The fibrillin-1 gene (FBN1), also known as FBN, is located on chromosome 15 band q21.1 in humans. [1] The gene is 200 kb in size, has 65 exons and encodes the 250 kDa protein fibrillin-1. [2] Fibrillin-1 is one of three isoforms of fibrillin and is the major structural protein of microfibrils. In addition to structural functions in microfibrils, FBN1 also has functions in homeostasis of various tissues. [3] Mutations of the gene can result in various diseases, such as Marfan syndrome.......

[1] Magenis, R.E., Maslen, C. L., Smith, L., Allen, L., Sakai, L. Y. (1991). Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1. Genomics 11/2, 346–351.
[2] Biery, N. J., Eldadah, Z. A., Moore, C. S., Stetten, G., Spencer, F., Dietz, H. C. (1999). Revised genomic organization of FBN1 and significance for regulated gene expression. Genomics 56/1, 70–77.
[3] Sherratt, M. J., Wess, T. J., Baldock, C., Ashworth, J., Purslow, P. P., Shuttleworth, C. A., Kielty, C. M. (2001). Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. Micron 32/2, 185–200.

### hackMD
hackMD tutorial https://hackmd.io/c/tutorials/%2Fs%2Ftutorials

## Slides, Materials
https://www.dropbox.com/s/br98zraya0mcymg/Unit1.pdf?dl=0
https://www.dropbox.com/sh/8rmmytkivtlk2x8/AABbU6dQBSb3HJLVihlIupRGa?dl=0
https://www.dropbox.com/s/br98zraya0mcymg/Unit1.pdf?dl=0
https://www.dropbox.com/sh/x8ocgfjhzu6ogvm/AAD-L_n2mQY35oe5VsqbOfJ1a?dl=0
https://www.dropbox.com/sh/ofke99mi0jqitoj/AABaAuc4LVW4GEhZaQmZQz2ma?dl=0&preview=Tasks_Week_2.docx

## Links
https://www.youtube.com/watch?v=gG7uCskUOrA

The Simple Club:
https://www.youtube.com/watch?v=Fy_3gpIkoNs
https://www.youtube.com/watch?v=HSdK7l9Qk1w
https://www.youtube.com/watch?v=3wFfj6D0_nQ

Intro lecture, recorded:
https://youtu.be/x5HuhXHPrRs

Links
Download sequences, NCBI Tutorial 3 Min!
https://youtu.be/ZWnLyYKozaI

How to organise your sequences with a “Sequence editor”, tutorial for ApE - 3 parts, 5 minutes each
https://youtu.be/G-6jiKbZTcs
https://youtu.be/dNc_7Cg1qiI
https://youtu.be/h4PiBcnRP2k

Watch me find homologs with ENSEMBL
https://www.loom.com/share/ffda5cb0a5934b538f88c88d70f10576

https://www.loom.com/share/f442e612e5d44660ba34f00cdd1da6b2

## HOMEWORK
Write 5 "Big picture"-sentences (first sentence of the opening paragraph) for the your protein/topic of interest. (Open-ended question, Bold statement, Quote, Personal Story, Imagine a brighter future).

Share the best of them tomorrow in class and comment what you like and maybe why the other examples did not work.
Get feedback from peers.

- The effects of Marfan syndrome and COVID-19 on the lungs and breathing are underrecognized despite the high morbidity that can occur.
- Marfan syndrome is a disease whose connective tissue complications can occur at any age.
- FBN1 is a gene that is notable for causing a wide range of connective tissue diseases in mutated form.
- Fibrillin-1 is the most important fibrillin and essential for the correct structure of human connective tissue.