genomics

Epigenetics and Epigenomics

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The human DNA sequence has been read, now we know how the genome works and how to detect and cure genetic diseases, don’t we?

Unfortunately not – or fortunately if you are working in this area. While we know the sequence of bases for a number of reference and other genomes, not only are we far from knowing and understanding all the variations that can be found between different people and the consequences of the variations – but there are also other layers of information in the genome that we are only starting to understand. I am talking about the field of epigenetics here, which looks at molecular “tags” that are attached to the DNA at certain places and play a key role in activation or deactivation of the genes in these places. In contrast to the actual DNA sequence these markers are reversible and get altered during embryonic development and differentiation, i.e. when cells develop into a specific cell types, e.g. a skin cell. They also get modified in a less fortunate way as we get old and in certain disease conditions such as diabetes, inflammation or cancer. The study of these tags  is called epigenetics, or epigenomics when applied to the entire human genome.

More specifically, these tags are molecular modifications, mostly methyl-groups that can be attached usually to the Cytosil DNA base and to histones, the proteins that the DNA is wrapped around to “get in shape”.

Sources and useful links:

health

Vaccination of newborns

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Most of us take vaccinations for granted and rely on them from our very first days. The whooping cough as an example can be deadly, especially for young babies who are too young to be protected by their own vaccination. Since 2010, the Centers for Disease Control and Prevention (CDC) has recorded between 10,000 and 50,000 cases each year in the United States and up to 20 babies dying. One recent study showed that many whooping cough deaths among babies could be prevented if all babies received the first dose of vaccination on time at 2 months old, when they are old enough to get vaccinated (CDC). Still, some parents believe they know better and risk their children’s life by not vaccinating them at all.

For the US the CDC recommends vaccination of newborns / babies against the following diseases:

For Germany the situation is almost the same and the following vacciantions are recommended for babies under 2 years:

  • Hib H. influenzae Typ b
  • Diphtherie
  • Hepatitis B
  • Masern
  • Mumps
  • Pertussis (Keuchhusten)
  • Pneumokokken
  • Poliomyelitis (Kinderlaehmung)
  • Röteln
  • Tetanus
  • Rotaviren
  • Varizellen (Windpocken)
  • Meningokokken C

Sources: CDCRobert-Koch-Institut

health

Genetic Conditions Screened in Newborns

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As part of the health assessment of newborn babies, a test for common genetic conditions is done by drawing a few drops of blood from the heel of the baby and sending this off for analysis. Any positive results will then be followed up by confirmatory test and a treatment can be initiated if required. The conditions are mostly life-threatening or disabling for the child if undiagnosed or left untreated.Below is a list of conditions that are screened as part of the current standard panel of core conditions and secondary conditions in the US-american health system. Secondary conditions are results that will be additionally (unintentionally) revealed when testing for the core conditions. If desired there are even more options for testing (supplemental screening). What test are offered or paid for depends on the state and the insurance. This information is taken from babysfirsttest.org.

1. Metabolic Disorders

ORGANIC ACID CONDITIONS

  • 2-Methyl-3-Hydroxybutyric Acidemia (2M3HBA)
  • 2-Methylbutyrylglycinuria (2MBG)
  • 3-Hydroxy-3-Methylglutaric Aciduria (HMG) *
  • 3-Methylcrotonyl-CoA Carboxylase Deficiency (3-MCC) *
  • 3-Methylglutaconic Aciduria (3MGA)
  • Beta-Ketothiolase Deficiency (BKT) *
  • Ethylmalonic Encephalopathy (EME)
  • Glutaric Acidemia, Type I (GA-1) *
  • Holocarboxylase Synthetase Deficiency (MCD)
  • Isobutyrylglycinuria (IBG)
  • Isovaleric Acidemia (IVA) *
  • Malonic Acidemia (MAL)
  • Methylmalonic Acidemia (Cobalamin Disorders) (Cbl A,B) *
  • Methylmalonic Acidemia (Methymalonyl-CoA Mutase Deficiency) (MUT) *
  • Methylmalonic Acidemia with Homocystinuria (Cbl C, D, F)
  • Propionic Acidemia (PROP) *

FATTY ACID OXIDATION DISORDERS

  • 2,4 Dienoyl-CoA Reductase Deficiency (DE RED)
  • Carnitine Acylcarnitine Translocase Deficiency (CACT)
  • Carnitine Palmitoyltransferase I Deficiency (CPT-IA)
  • Carnitine Palmitoyltransferase Type II Deficiency (CPT-II)
  • Carnitine Uptake Defect (CUD) *
  • Glutaric Acidemia, Type II (GA-2)
  • Long-Chain L-3 Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD) *
  • Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) *
  • Medium-Chain Ketoacyl-CoA Thiolase Deficiency (MCAT)
  • Medium/Short-Chain L-3 Hydroxyacyl-CoA Dehydrogenase Deficiency (M/SCHAD)
  • Short-Chain Acyl-CoA Dehydrogenase Deficiency (SCAD)
  • Trifunctional Protein Deficiency (TFP) *
  • Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD) *

AMINO ACID DISORDERS

  • Argininemia (ARG)
  • Argininosuccinic Aciduria (ASA) *
  • Benign Hyperphenylalaninemia (H-PHE)
  • Biopterin Defect in Cofactor Biosynthesis (BIOPT-BS)
  • Biopterin Defect in Cofactor Regeneration (BIOPT-REG)
  • Carbamoyl Phosphate Synthetase I Deficiency (CPS)
  • Citrullinemia, Type I (CIT) *
  • Citrullinemia, Type II (CIT II)
  • Classic Phenylketonuria (PKU) *
  • Homocystinuria (HCY) *
  • Hypermethioninemia (MET)
  • Hyperornithine with Gyrate Deficiency (Hyper ORN)
  • Maple Syrup Urine Disease (MSUD) *
  • Nonketotic Hyperglycinemia (NKH)
  • Ornithine Transcarbamylase Deficiency (OTC)
  • Prolinemia (PRO)
  • Tyrosinemia, Type I (TYR I) *
  • Tyrosinemia, Type II (TYR II)
  • Tyrosinemia, Type III (TYR III)

 

2. Endocrine Disorders

  • Congenital Adrenal Hyperplasia (CAH) *
  • Primary Congenital Hypothyroidism (CH) *

 

3. Hemoglobin Disorders

  • Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD)
  • Hemoglobinopathies (Var Hb)
  • S, Beta-Thalassemia (Hb S/ßTh) *
  • S, C Disease (Hb S/C) *
  • Sickle Cell Anemia (Hb SS) *

 

4. Other Disorders

  • Adrenoleukodys-trophy (ALD)
  • Biotinidase Deficiency (BIOT) *
  • Classic Galactosemia (GALT) *
  • Congenital Toxoplasmosis (TOXO)
  • Critical Congenital Heart Disease (CCHD) *
  • Cystic Fibrosis (CF) *
  • Formiminoglutamic Acidemia (FIGLU)
  • Galactoepimerase Deficiency (GALE)
  • Galactokinase Deficiency (GALK)
  • Hearing loss (HEAR)
  • Human Immunodeficiency Virus (HIV)
  • Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (HHH)
  • Pyroglutamic Acidemia (5-OXO)
  • Severe Combined Immunodeficiency (SCID) *
  • T-cell Related Lymphocyte Deficiencies

 

5. Lysosomal Storage Disorders

  • Fabry (FABRY)
  • Gaucher (GBA)
  • Krabbe
  • Mucopolysaccharidosis Type-I (MPS I)
  • Mucopolysaccharidosis Type-II (MPS II)
  • Niemann-Pick Disease (NPD)
  • Pompe (POMPE)

See more at: www.babysfirsttest.org

bioinformatics

Software Requirements Specification

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For any large software project (i.e. one that requires more than a few scripts performing a one-off task) and for every project that was initiated by a customer request, it is useful to precisely define the requirements before starting to write any code. This might be painful at times and slow down the coding fun, but it should avoid a lot of frustration on either side in the end.

Here is a short summary of what Software Requirements Specification (SRS) (IEEE 830) are, how to write them, what they are good for.

SRS is a complete description of the behavior of a system to be developed, including use cases.

The benefits of writing specifications when planning a software project are:

  • Establish the basis for agreement between the customers and the suppliers on what the software product is to do.
  • Reduce the development effort by avoiding redesign, recoding, and retesting and revealing omissions, misunderstandings, and inconsistencies early in the development cycle.
  • Provide a basis for estimating costs and schedules.
  • Provide a baseline for validation (comparison against what the customer needs) and verification (comparison with the formal specifications).
  • Facilitate transfer to new users or new machines.
  • Serve as a basis for enhancement.

Key points to address:

  • Required functionality.
  • External interfaces.
  • Performance.
  • Attributes.
  • Design constraints imposed on an implementation.

Avoid design details and coding details in the specs. Hardware requirements etc. go into general System Specifications, not SRS. The content and language of the document should fit the description with the following key words:

Complete, Consistent, Accurate, Modifiable, Ranked, Testable, Traceable, Unambiguous, Valid, Verifiable

Descriptions of “use cases”, mock-up GUI components and other visual aids are extremely useful to communicate with the parties involved.

Sources:
Wikipedia
www.microtoolsinc.com
www.techwr-l.com

bioinformatics

BCL files

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As part of the Primary Analysis Illumina sequencing machines measure the intensity of the channels used for encoding the different bases and identify the most likely base at a given position of a sequencing read (tag). The Real Time Analysis (RTA) software writes the base and the confidence in the call as a quality score to base call (.bcl) files. As the name implies this is done in real time, i.e. for every cycle of the sequencing run a call for every location identified on the flow cell (tiles and lanes) is added. Bcl files are stored in binary format and represent the raw data output of a sequencing run. The format is described here. Software such as Casava/BclToFastq, Eland or the iSAAC aligner can make use of these files.

The *.bcl files are stored in the BaseCalls directory:

<run directory>/Data/Intensities/BaseCalls/L<lane>/C<cycle>.1

They are named in the format:

s_<lane>_<tile>.bcl

If you want to overcome errors during downstream processing from missing calls, software such as iSAAC and configureBclToFastq have an “–ignore-missing-bcl” command line option. This will interpret missing *.bcl files as no call (N) at that position.

Sources: Illumina, SeqAnswers