Center for Integrative Genomics, University of Lausanne, Switzerland

Two postdoctoral positions (2 years with possible extensions up to 5 years) are available immediately in the evolutionary genomics group of Henrik Kaessmann.

We are seeking highly qualified and enthusiastic applicants with strong skills in computational biology/bioinformatics, preferably also with experience in data mining and comparative or evolutionary genome analysis.

We have been interested in a range of topics related to the functional evolution of genomes from primates (e.g., the emergence of new genes and their functions) and other mammals (e.g., the origin and evolution of mammalian sex chromosomes). In the framework of a recently launched series of projects, a large amount of transcriptome and genome (e.g., epigenome) data are being produced by the wet lab unit of the group using next generation sequencing technologies for a unique collection of tissues from representative mammals and outgroup species (e.g., birds). Topics of current projects based on these data include the origins and/or evolution of protein-coding genes, alternative splicing, microRNAs, long noncoding RNAs, and dosage compensation.

The postdoctoral fellow will perform integrated evolutionary/bioinformatics analyses based on data produced in the lab and available genomic data. The specific project will be developed together with the candidate.

The language of the institute is English, and its members form an international group that is rapidly expanding. The institute is located in Lausanne, a beautiful city at Lake Geneva.

For more information on the group and our institute more generally, please refer to our website: http://www.unil.ch/cig/page7858_en.html

Please submit a CV, statement of research interest, and names of three references to: Henrik Kaessmann (Henrik.Kaessmann@unil.ch).

Webpage : http://www.unil.ch/cig/page7858.html

What Are piRNAs?

piRNAs are the largest class of small non-coding RNAs, typically 24–32 nucleotides in length. Unlike microRNAs (miRNAs) and small interfering RNAs (siRNAs), piRNAs do not rely on Dicer enzymes for maturation. Instead, they are processed from long single-stranded precursors and associate with PIWI proteins, a subclass of the Argonaute protein family.

The primary functions of piRNAs include:

1. Silencing Transposable Elements: By targeting transposons, piRNAs prevent genomic instability, particularly in germline cells.
2. Regulating Gene Expression: piRNAs modulate gene expression at transcriptional and post-transcriptional levels.
3. Epigenetic Modulation: They guide epigenetic modifications, such as DNA methylation, to specific genomic loci.

Challenges in piRNA Research

Studying piRNAs is fraught with challenges, including:

• Short Length: Their small size complicates sequencing and alignment.
• Lack of Sequence Conservation: Unlike miRNAs, piRNAs exhibit limited sequence conservation across species.
• Complex Biogenesis: The intricate pathways of piRNA generation require sophisticated computational tools to unravel.

Bioinformatics: Illuminating the World of piRNAs

Bioinformatics has emerged as an indispensable tool for studying piRNAs, facilitating their discovery, annotation, and functional analysis. Here's how bioinformatics is transforming piRNA research:

1. Identification and Annotation

The discovery of piRNAs relies on next-generation sequencing (NGS) data. Bioinformatics tools such as piRNApredictor and Piano identify piRNA clusters and predict potential targets. Databases like piRBase and piRNAdb curate information about known piRNAs, their sequences, and associated proteins.

2. Mapping and Alignment

piRNAs often originate from repetitive regions, making their alignment challenging. Tools like Bowtie and STAR handle the unique mapping requirements of piRNAs, enabling accurate identification of piRNA clusters in genomes.

3. Functional Analysis

Bioinformatics approaches predict piRNA functions by analyzing their interactions with transposons, genes, and epigenetic marks. Algorithms such as TargetFinder and RIblast explore piRNA-mRNA interactions, shedding light on regulatory networks.

4. Evolutionary Studies

piRNAs are evolutionarily diverse, reflecting their roles in species-specific genomic defense. Comparative genomics tools help trace the evolution of piRNA clusters and their associated PIWI proteins across species.

5. Epigenomic Insights

piRNAs are key players in epigenetic regulation. Bioinformatics pipelines integrate piRNA data with chromatin immunoprecipitation sequencing (ChIP-seq) and DNA methylation data to uncover their role in shaping the epigenome.

Case Study: piRNAs in Germline Integrity

One of the hallmark functions of piRNAs is the suppression of transposable elements in the germline. For example, in Drosophila melanogaster, piRNAs target retrotransposons like gypsy and copia. Bioinformatics analyses revealed that these piRNAs guide PIWI proteins to transposon-derived RNA, ensuring genome stability during gametogenesis.

Clinical Relevance of piRNAs

Recent studies suggest that piRNAs may serve as biomarkers for diseases such as cancer, infertility, and neurodegenerative disorders. For instance:

• Cancer: Dysregulated piRNA expression has been linked to tumorigenesis, making them potential targets for cancer therapies.
• Infertility: Aberrant piRNA pathways are implicated in male infertility due to their role in spermatogenesis.
• Neurodegeneration: piRNAs may regulate neuronal gene expression, highlighting their potential in neurological research.

Future Directions

The integration of bioinformatics with emerging technologies offers exciting opportunities for piRNA research:

• Single-Cell Sequencing: Unveiling cell-specific piRNA expression and function.
• Machine Learning: Predicting piRNA functions and targets with greater accuracy.
• CRISPR-Based Tools: Editing piRNA clusters to explore their roles in vivo.

Conclusion

piRNAs are the unsung guardians of the genome, safeguarding genetic material from transposable elements and contributing to gene regulation and epigenetic programming. Bioinformatics has opened the floodgates of discovery, unraveling the complexities of piRNAs and their myriad roles in biology and disease.

As we continue to decode the piRNA landscape, these small RNAs promise to unveil big secrets about genome stability, evolution, and human health, cementing their place as a fascinating frontier in molecular biology.

Introduction to bioinformatics is a course for biologists and clinicians that would like to learn more about the way bioinformatics is used in healthcare, biotech and pharmaceuitcal industry as well as basic research. The course covers many of the topics transformed by the emergence of big data and computational technologies. To learn more about the course, visit: https://edu.t-bio.info/course/introduction-bioinformatics/

Gene expression and protein expression patterns between normal and non-normal tissues is a growing area of research that may lead to the identification of candidate genes for understanding the etiology of common, complex diseases.

Lab homepage @ http://ritchielab.psu.edu/ritchielab/

https://liulab-dfci.github.io/software/

Lab Page http://gabi.cidbio.org/index/

ALF
A Simulation Framework for Genome Evolution
http://www.cbrg.ethz.ch/alf

Bayesian Serial SimCoal
Bayesian Serial SimCoal, (BayeSSC) is a modification of SIMCOAL 1.0, a program written by Laurent Excoffier, John Novembre, and Stefan Schneider.
http://www.stanford.edu/group/hadlylab/ssc/index.html

BEERS
BEERS was designed to benchmark RNA-Seq alignment algorithms and also algorithms that aim to reconstruct different isoforms and alternate splicing from RNA-Seq data
http://cbil.upenn.edu/beers/

BOTTLENECK
Bottleneck is a program for detecting recent effective population size reductions from allele data frequencies
http://www.ensam.inra.fr/urlb/bottleneck/bottleneck.html

BottleSim
BottleSim is a computer simulation program for simulating the process of population bottlenecks
http://chkuo.name/software/bottlesim.html

CASS
Protein Sequence Simulation
http://www.wyomingbioinformatics.org/liberlesgroup/cass/

CDPOP
CDPOP is a landscape genetics tool for simulating the emergence of spatial genetic structure in populations resulting from specified landscape processes governing organism movement behavior.
http://cel.dbs.umt.edu/cdpop

CoalFace
CoalFace is a simulation of the coalescent process with the visual display of gene genealogies.
http://web.up.ac.za/default.asp?ipkcategoryid=3283

CoaSim
CoaSim is a tool for simulating the coalescent process with recombination and geneconversion under various demographic models.
http://users-birc.au.dk/mailund/coasim/index.html

cosi
The cosi package is written in C and is available as a tar file.
http://www.broadinstitute.org/~sfs/cosi/

CS-PSeq-Gen
A program to simulate the evolution of protein sequences under the constraints of the information of a particular reconstructed phylogeny
http://bioserv.rpbs.univ-paris-diderot.fr/software/cs-pseq-gen.html

DAWG
An application designed to simulate the evolution of recombinant DNA sequences in continuous time
http://scit.us/projects/dawg

Easypop
EASYPOP is an individual based model intended to simulate datasets under a very broad range of conditions
http://www.unil.ch/dee/page36926_fr.html

EggLib
EggLib is a C++/Python library and program package for evolutionary genetics and genomics.
http://egglib.sourceforge.net/

EvolSimulator
A simulation test bed for hypotheses of genome evolution
http://acb.qfab.org/acb/evolsim/

EvolveAGene
A realistic coding sequence simulation program that separates mutation from selection and allows the user to set selection conditions
http://bellinghamresearchinstitute.com/software/index.html

fastsimcoal
A continuous-¬‐time coalescent simulator of genomic diversity under arbitrarily complex evolutionary scenarios
http://cmpg.unibe.ch/software/fastsimcoal/

FastSLINK
Simulation of Marker and Phenotype Data in Pedigrees
http://watson.hgen.pitt.edu/

FFPopSim
C++/Python library for population genetics.
http://webdav.tuebingen.mpg.de/ffpopsim/

FLUX SIMULATOR
The Flux Simulator aims at providing a deterministic in silico reproduction of the experimental pipelines for RNA-Seq, employing a minimal set of parameters.
http://flux.sammeth.net/simulator.html

ForSim
ForSim: A Forward Evolutionary Computer Simulation
http://www.anthro.psu.edu/weiss_lab/research.shtml

ForwSim
The program given below is based on the algorithm described in Padhukasahasram et al. 2008 to simulate genetic drift in a standard Wright-Fisher process.
http://badri-populationgeneticsimulators.blogspot.com/

FPG
Forward Population Genetic simulation
http://genfaculty.rutgers.edu/hey/software#fpg

FREGENE
FREGENE is a C++ program that simulates sequence-like data over large genomic regions in large diploid populations.
http://www.ebi.ac.uk/projects/bargen/download/fregen/documentation_html.html

GAMETES
Genetic Architecture Model Emulator for Testing and Evaluating Software: Simulates complex SNP models with pure, strict epistatic interactions with n-loci.
http://sourceforge.net/projects/gametes/?source=navbar

GASP
Genometric Analysis Simulation Program. A software tool for testing and investigating methods in statistical genetics by generating samples of family data based on user specified models.
http://research.nhgri.nih.gov/gasp/

GemSIM
Next generation sequencing read simulator
http://sourceforge.net/projects/gemsim/

GeneArtisan
Simulation of Markers in Case-Control Study Designs
http://www.rannala.org/?page_id=241

GENOME
A rapid coalescent-based whole genome simulator
http://www.sph.umich.edu/csg/liang/genome/

GenomePop2
GenomePop2 is a specialization of the program GenomePop just to manage SNPs under more flexible and useful settings. If you need models with more than 2 alleles please use the GenomePop program version.
http://webs.uvigo.es/acraaj/genomepop2.htm

GenomeSimla
GenomeSIMLA is currently under development- however, we have a beta release that we are asking to be tested
http://chgr.mc.vanderbilt.edu/genomesimla/

GENS2
Simulates interactions among two genetic and one environmental factor and also allows for epistatic interactions.
https://sourceforge.net/projects/gensim/

GWAsimulator
A rapid whole genome simulation program
http://biostat.mc.vanderbilt.edu/wiki/main/gwasimulator

HAP-SAMPLE
An association simulator for candidate regions or genome scans
http://www.hapsample.org/

HAPGEN
A simulator for the simulation of case control datasets at SNP markers
https://mathgen.stats.ox.ac.uk/genetics_software/hapgen/hapgen2.html

HapSim
A simulation tool for generating haplotype data with pre-specified allele frequencies and LD coefficients
http://cran.r-project.org/web/packages/hapsim/index.html

HAPSIMU
A program that simulates heterogeneous populations with various known and controllable structures under the continuous migration model or the discrete model
http://l.web.umkc.edu/liujian/

IBDsim
IBDSim is a computer package for the simulation of genotypic data under general isolation by distance models.
http://raphael.leblois.free.fr/

indel-Seq-Gen
A biological sequence simulation program that simulates highly divergent DNA sequences and protein superfamilies
http://bioinfolab.unl.edu/~cstrope/isg/

Indelible
A powerful and flexible simulator of biological evolution
http://abacus.gene.ucl.ac.uk/software/indelible/

invertFREGENE
InvertFREGENE is a forward-in-time simulator of inversions in population genetic data
http://www.ebi.ac.uk/projects/bargen/

kernalPop
A spatially explicit population genetic simulation engine
http://cran.r-project.org/src/contrib/archive/kernelpop/

MaCS
Markovian Coalescent Simulator
http://www-hsc.usc.edu/~garykche/

Mason
A package for the simulation of nucleotide data.
http://www.seqan.de/projects/mason/

mbs
modifying Hudson's ms software to generate samples of DNA sequences with a biallelic site under selection
http://www.sendou.soken.ac.jp/esb/innan/innanlab/software.html

Mendel's Accountant
Mendel's Accountant (MENDEL) is an advanced numerical simulation program for modeling genetic change over time and was developed collaboratively by Sanford, Baumgardner, Brewer, Gibson and ReMine
http://mendelsaccount.sourceforge.net/

MetaSim
A tool to generate collections of synthetic reads that reflect the diverse taxonomical composition of typical metagenome data sets
http://ab.inf.uni-tuebingen.de/software/metasim/

mlcoalsim
Multilocus Coalescent Simulations
http://code.google.com/p/mlcoalsim-v1/

ms
The purpose of this program is to allow one to investigate the statistical properties of such samples, to evaluate estimators or statistical tests, and generally to aid in the interpretation of polymorphism data sets.
http://home.uchicago.edu/~rhudson1/source/mksamples.html

msHOT
The purpose of this program is to allow one to investigate the statistical properties of such samples, to evaluate estimators or statistical tests, and generally to aid in the interpretation of polymorphism data sets.
http://home.uchicago.edu/~rhudson1/

msms
A coalescent Simlation tool with selection.
http://www.mabs.at/ewing/msms/index.shtml

MySSP
A program for the simulation of DNA sequence evolution across a phylogenetic tree
http://www.rosenberglab.net/software.php

Nemo
A forward-time, individual-based, genetically explicit, and stochastic simulation program designed to study the evolution of genetic markers, life history traits, and phenotypic traits in a flexible (meta-)population framework.
http://nemo2.sourceforge.net/

NetRecodon
Coalescent simulation of coding DNA sequences with recombination (inter and intracodon), migration and demography
http://code.google.com/p/netrecodon/

PEDAGOG
Software for simulating eco-evolutionary population dynamics
https://bcrc.bio.umass.edu/pedigreesoftware/node/5

phenosim
A tool to add phenotypes to simulated genotypes
http://evoplant.uni-hohenheim.de/doku.php?id=software:software

PhyloSim
An R package for the Monte Carlo simulation of sequence evolution
http://bit.ly/rlsim-git

pIRS
Profile-based Illumina pair-end reads simulator
https://code.google.com/p/pirs/

ProteinEvolver
Simulation of protein evolution along phylogenies under structure-based substitution models
http://code.google.com/p/proteinevolver/

QMSim
QTL and Marker Simulator
http://www.aps.uoguelph.ca/~msargol/qmsim/

quantiNEMO
An individual-based program for the analysis of quantitative traits with explicit genetic architecture potentially under selection in a structured population
http://www2.unil.ch/popgen/softwares/quantinemo/

RECOAL
Simulates new haplotype data from a reference population of haplotypes.
ftp://popgen.usc.edu/

Recodon
Coalescent simulation of coding DNA sequences with recombination, migration and demography
http://code.google.com/p/recodon/

rlsim
A package for simulating RNA-seq library preparation with parameter estimation
http://bit.ly/rlsim-git

Rmetasim
Rmetasim is a front-end for the metasim engine that is implemented as a package that runs in the statistical computing environment R
http://linum.cofc.edu/software.html#metasim

RNA Seq Simulator
RSS takes SAM alignment files from RNA-Seq data and simulates over dispersed, multiple replica, differential, non-stranded RNA-Seq datasets.
http://useq.sourceforge.net/cmdlnmenus.html#rnaseqsimulator

Rose
Random model of sequence evolution
http://bibiserv.techfak.uni-bielefeld.de/rose/

SelSim
SelSim is a program for Monte Carlo simulation of DNA polymorphism data for a recom- bining region within which a single bi-allelic site has experienced natural selection
http://www.well.ox.ac.uk/~spencer/selsim/

Seq-Gen
An application for the Monte Carlo simulation of molecular sequence evolution along phylogenetic trees.
http://tree.bio.ed.ac.uk/software/seqgen/

SEQPower
Statistical power analysis for sequence-based association studies
http://bioinformatics.org/spower/

SeqSIMLA
SeqSIMLA can simulate sequence data with user-specified disease and quantitative trait models. Family or unrelated case-control data can be simulated.
http://seqsimla.sourceforge.net/

Serial NetEvolve
A flexible utility for generating serially-sampled sequences along a tree or recombinant network
http://biorg.cis.fiu.edu/sne/

SFS_CODE
SFS_CODE can perform forward population genetic simulations under a general Wright-Fisher model with arbitrary migration, demographic, selective, and mutational effects.
http://sfscode.sourceforge.net/sfs_code/index/index.html

SIBSIM
Quantitative phenotype simulation in extended pedigrees
http://sourceforge.net/projects/sibsim/

SIMCOAL2
A coalescent program for the simulation of complex recombination patterns over large genomic regions under various demographic models
http://cmpg.unibe.ch/software/simcoal2/

SimCopy
An R package simulating the evolution of copy number profiles along a tree.
http://bit.ly/simcopy

SIMLA
SIMLA is a SIMuLAtion program that generates data sets of families for use in Linkage and Association studies.
http://www.chg.duke.edu/research/simla.html

SimPed
A Simulation Program to Generate Haplotype and Genotype Data for Pedigree Structures
http://www.hgsc.bcm.tmc.edu/content/simped

Simprot
A program to simulate protein evolution by substitution, insertion and deletion
http://www.uhnresearch.ca/labs/tillier/software.htm#3

SimRare
Rare variant simulation and analysis tool
http://code.google.com/p/simrare/

simuGWAS
A forward-time simulator that simulates realistic samples for genome-wide association studies.
http://simupop.sourceforge.net/cookbook/simucomplexdisease

simuPOP
simuPOP is a general-purpose individual-based forward-time population genetics simulation environment.
http://simupop.sourceforge.net/

SISSI
A software tool to generate data of related sequences along a given phylogeny, taking into account user defined system of neighbourhoods and instantaneous rate matrices.
http://www.cibiv.at/software/sissi/

SNPsim
Coalescent simulation of hotspot recombination
http://code.google.com/p/phylosoftware/

SPIP
SPIP simulates the transmission of genes from parents to offspring in a population having demographic structure defined by the user
http://swfsc.noaa.gov/textblock.aspx?division=fed&id=3434

Splatche
Spatial and Temporal Coalescences in Heterogeneous Environment
http://www.splatche.com/

srv
Simulator of Rare Varaints (srv) is a simulator for the simulation of the introduction and evolution of (rare) genetic variants.
http://simupop.sourceforge.net/cookbook/simurarevariants

SUP
SLINK/FastSLINK utility program
http://mlemire.freeshell.org/software.html

TreesimJ
A flexible, forward-time population genetic simulator
http://code.google.com/p/treesimj/

Vortex
VORTEX is an individual-based simulation model for population viability analysis (PVA).
http://www.vortex9.org/vortex.html

References:

Image www.evolution-of-life.com

www.cancer.gov

Genome Workbench can display sequence data in many ways, including graphical sequence views, various alignment views, phylogenetic tree views, and tabular views of data. It can also align your private data to data in public databases, display your data in the context of public data, and retrieve BLAST results.

Genome Workbench is built on the NCBI C++ ToolKit and uses cross-platform APIs for graphics. It runs on your local machine, and is available for Windows 2000/XP, Linux, MacOS X, and various flavors of Unix.

NCBI Genome Workbench is an integrated application for viewing and analyzing sequence data. Genome Workbench was developed entirely in-house at NCBI and makes use of the NCBI C++ ToolKit. The C++ ToolKit provides a convenient and flexible cross-platform API for managing system internals, database connections, network sockets, and the NCBI data model. In addition, the C++ ToolKit provides the Object Manager, which abstracts handling of sequences and sequence-related objects.

 New Features in Genome Workbench 2.7.15

• Multiple Alignment View: implemented adaptive feature display when zooming in
• Active Objects Inspector replaces Selection Inspector. New View should offer an improved selection context examination. See Using Active Objects Inspector tutorial for more details.
• Binary packages for Linux OpenSUSE 13.1 are now available

Bug Fixes and Improvements in Genome Workbench 2.7.15

• Fixed major issue with OpenGL overlay/scrolling. Could cause crashes or view scrolling irregularities
• Multiple Pane View: fixed crash on loading BLAST results
• Graphical Sequence View: fixed crash on zooming in and out, related to SNP track
• Graphical Sequence View: fixed Go To Position dialog to give better diagnostics in case of a user error
• Graphical Sequence View: PDF export fixed rendering of Markers with commas in the name
• Text View / Flat File: fixed Mac OS rendering issues
• Text View / Flat File: performance optimization, extended capabilities of real-time rendering of molecules to tens of thousands
• File Import: optimization improvement to speed up load of files containing multiple project items
• File Import: remapping stage now shows accession.version and description of molecules, instead of plain GI numbers
• Mac OS: improved tooltips for toolbar buttons
• Phylogenetic Tree Builder Tool: improved diagnostics of errors
• Multiple Alignment View: optimizations to avoid main GUI freezes
• Open Dialog: removed duplicate elements in table of genomes (load Genome)
• PDF export: fixed issue with XREF table errors
• Tree View: fixed issues with showing Force Layout progress on Mac OS
• Tree View: PDF export fixed issues for showing labels of collapsed nodes
• Tree View: added an option to stop layout
• Tree View: broadcasting mechanism fixed not to accumulate selected nodes

Reference:

NCBI news

http://www.ncbi.nlm.nih.gov/tools/gbench/

• hist: Create an histogram of k-mer occurrences from a sequence file. Adds metadata in output for easy plotting.
• gcp: K-mer GC Processor. Creates a matrix of the number of K-mers found given a GC count and a K-mer count.
• comp: K-mer comparison tool. Creates a matrix of shared K-mers between two (or three) sequence files or hashes.
• sect: SEquence Coverage estimator Tool. Estimates the coverage of each sequence in a file using K-mers from another sequence file.
• blob: Given, reads and an assembly, calculates both the read and assembly K-mer coverage along with GC% for each sequence in the assembly.SEquence Coverage estimator Tool.
• filter: Filtering tools. Contains tools for filtering k-mer hashes and FastQ/A files:
  • kmer: Produces a k-mer hash containing only k-mers within specified coverage and GC tolerances.
  • seq: Filters a sequence file based on whether or not the sequences contain k-mers within a provided hash.
• plot: Plotting tools. Contains several plotting tools to visualise K-mer and compare distributions. The following plot tools are available:
  • density: Creates a density plot from a matrix created with the "comp" tool. Typically this is used to compare two K-mer hashes produced by different NGS reads.
  • profile: Creates a K-mer coverage plot for a single sequence. Takes in fasta coverage output coverage from the "sect" tool
  • spectra-cn: Creates a stacked histogram using a matrix created with the "comp" tool. Typically this is used to compare a jellyfish hash produced from a read set to a jellyfish hash produced from an assembly. The plot shows the amount of distinct K-mers absent, as well as the copy number variation present within the assembly.
  • spectra-hist: Creates a K-mer spectra plot for a set of K-mer histograms produced either by jellyfish-histo or kat-histo.
  • spectra-mx: Creates a K-mer spectra plot for a set of K-mer histograms that are derived from selected rows or columns in a matrix produced by the "comp".

In addition, KAT contains a python script for analysing the mathematical distributions present in the K-mer spectra in order to determine how much content is present in each peak.

This README only contains some brief details of how to install and use KAT. For more extensive documentation please visit: https://kat.readthedocs.org/en/latest/

https://academic.oup.com/bioinformatics/article/33/4/574/2664339 

Address of the bookmark: https://github.com/TGAC/KAT

Address of the bookmark: https://github.com/rhysf/Synima