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I'm at the 2017 Bioinformatics Open Source Conference (BOSC) in Prague. These are my notes from the day 2 morning sessions, including the epigenetic personalized medicine keynote, community building, citizen science and late breaking talks.

BOSC is a two day annual conference organized by the Open Bioinformatics Foundation. It's an open community interested in building reusable and interoperable tools for doing biological research. All video from these presentations will be available from the schedule page and slides from the f1000 channel.

ISMB keynote

Bioinformatics for Personalized Medicine: Looking Beyond the Genome

Christoph Bock

Talk focuses on how the epigenome will impact personalized medicine. Most drugs only help a fraction of people, because each patient has an individualized molecular background. In cancer, standard of care right now includes gene panel or targeted sequencing to match patients to therapies. Many more challenges ahead to integrate multiple data types, model heterogeneity and quantify and propagate prediction confidence.

Research focus is epigenomic alterations: methylation, chromatin marks. Builds off cancer genetics looking at driver and passenger mutations. At the next level, inherited epigenomic reprogramming including complex interactions with the genetics.

Focus is on Ewan sarcoma, an aggressive bone tumor in children. It is genetically simple cancer, driven by a single EWS-ETS gene fusion event with few additional alterations. Hypothesis is that epigenetic heterogeneity may explain clinical response heterogeneity. Used bisulfite sequencing. As a first pass, unsupervised methods found no useful clinical relationships. Nathan Sheffield dug further into the data, developing a method for finding regulatory footprints from methylation. Outcome: has a epigenetic signature of initial cell type.

Second example, cancers of unknown primary site. Profile tumor samples and try to use methylation marks to predict the initial site of the tumor. This has validated clinical utility, taking 5 years to reproduce and translate to clinic. Next step is a clinical trial, but promising step for better assigning therapies. So, cells contain an epigenetic record of development history and can use to improve treatments.

Next steps are to try and define an epigenetic landscape over time. International Human Epigenome Consortium (IHEC): 1000 reference genomes covering cells over entire human body. Can we use this to infer differentiation hierarchies from epigenetic data. Can infer computational lineage tree that matches FACS sorted manual work demonstrated using blood differentiation. LOLA: bioconductor package that provides GSEA like method for genomic region BED files, used to differentiate cell types. Lots of great tool development from the lab.

Second example: using these methods to stratify leukemia patients -- chromatin signatures associated with different disease subtypes. Chromatin data gives principal components capturing the variability in the disease, placing patients on a landscape. Idea of a progression zone, how they change over time. Incredibly useful analogs to genetic heterogeneity analysis. Cancer, and biology in general, is staggeringly complex.

Next idea, how do drugs modify the chromatin/epigenetic landscape. Try to model using CRISPR for high throughput epigenomic editing. Problem: need to introduce 1000s of alterations into cancer cells. Approach: CRISPR single cell screening: CRISPR library, infect in bulk, apply drug/virus stimulus, perform single cell RNA-seq, link transcriptome to CRISPR alteration. Method is CROP-seq. Similar to Perturb-Seq which uses an expressed barcode to tag the gRNA. CROP-seq meant to scale beyond thousands of samples. Brilliantly open work with protocols available online.

Summary: epigenomic marks are generalization of cell type, capturing development history and future potential of cells. Prediction methods to understand require embracing and understading complexity. Practical clinical work: keeping patients out of danger zone of disease progression. Need to engage the patients: this is a cornerstone for personalized medicine. So nice to see discussion of citizen science, open discussion and focus on education.

Community Building and Citizen Science

BeerDeCoded: exploring the beer metagenome

Jonathan Sobel

BeedDeCoded is a personal project aimed at a general audience. Project at the cool Hackuarium hackerspace in Lausanne. Idea is to work with drinkers, homebrewers and microbreweries. Trying to engage at festivals and events -- it's a way to engage with the public and discuss issues around DNA sequencing. Crowdfunded on Kickstarter to fund the project: nominate a beer, sample it, use BentoLab to prepare and sequence with Nanopore MinION. Did beer extraction workshops. Practically, aligned against ITS database. All analysis and code on GitHub. Results: found higher variety of specifies in complex fermented beers. Visualized with cluster plot of beers and organisms. Nice example of making science accessible to the public in an interesting way.

Supporting curation communities & collecting technical dividends

Monica Munoz-Torres

Apollo is a great curation tool for improving genome representations. It's a multi-user, graphical web application for edit and improve annotations. It's also a social network for curators. On the architecture side, uses jBrowse and then communicates with a backend Apollo server. It now has a web services API that interacts with Galaxy. Idea is to have more genomes with better annotations and have a great user base using Apollo for this. Curation improves when there is dialog between and within communities. Tons of great examples of different genome communities working with Apollo, from Koalas to Heliconius butterfies to Arthropods. Communities are both users and contributing back to Apollo code base.

Journal of Open Source Software (JOSS)

Pjotr Prins

The Journal of Open Source Software (JOSS) initiated based on observation that software developers need a track record of publication. However most software developers don't focus on this since it ends up being less of a priority next to coding, developing and documenting. Code is often a better demonstration of a project than a paper. JOSS is all on GitHub and papers are short descriptions of the software. JOSS review process is lightweight, fast, free and public. It's fully indexed and a real journal. Important point made during Q/A: DOIs don't mean anything with regards to being peer reviewed.

Building an open, collaborative, online infrastructure for bioinformatics training

Bérénice Batut

There is an increasing demand for learning bioinformatics. Currently happens through informal training but surveys show most would prefer online or local training options. Galaxy is a nice scalable platform to get folks to learn bioinformatics. Galaxy Training Network aggregates training resources, more than a registered event per month over the past few years so lots of ongoing training with this work worldwide. Difficulties: hard to keep up with improvements and changes to Galaxy and tools. Established a shared online set of tutorials. Very nice markdown to tutorial HTML process. Also collecting easy to use small datasets for tutorials. Includes required tools in Galaxy needed for each tutorial to make it easier to install and setup. They've really thought through all of the shared pain of building up training materials. Galaxy training materials all available from TESS and tagged with metadata. Incredible resource to help with scaling teaching to meet the needs of researchers.

Software and social strategies for community sourced biological networks and ontologies

Dexter Pratt

Aim is to get more and better exper content by engaging with the community. NDEx is infrastructure for finding ontologies and other networks. Idea is to engage lab researchers to keep things up to date. Not just curators to have user driven content with discussion. Idea is to create topic focused communities using social strategies to motivate: making it easy to publish by providing collections of networks. Provide full provenance and adding automation to improve networks and ease burden on researchers.

Distance-based, online bioinformatics training in Africa: the H3ABioNet experience

Nicola Mulder

H3ABioNet builds infratructure for Africa, talking about fulfilling the need for basic bioinformatics training for scientists. Provide a distributed classrooms models, with pre-recorded lectures and practical assignments. All material is creative commons and freely available. Used in a variety of classrooms across Africa -- interact within classes and also between locations. Provides virtual classrooms and live sessions. Amazing interactivity and scalability.

Late-Breaking Lightning Talks

Recent object formation in the core of Galaxy

Martin Cech

An update on the work in the Galaxy community in the past year. Martin shows an amazing list of public Galaxy servers, focuses on internationalization work. Emphasizes the reproducibility stack with bioconda and biocontainers: deprecated the Galaxy package manager in favor of bioconda. Jupyter based notebooks embedded inside Galaxy. Other interactive tools: Phinch, RStudio, Neo4j. An incredible ecosystem of diverse users.

Reproducibility of computational workflows is automated using continuous analysis

Brett Beaulieu-Jones

Nice followup on a preliminary talk at BOSC 2017, focusing on how to improve reproducibility of workflows. Big issue, half of papers don't cite version of software used. Continuous analysis provides a continuous integration based approach to running analyses. Provides reproducibility and can see changes of analysis over time. Can share audit logs even if can't share original data. Great analysis with Geisinger health on 750k patients how a code change influenced results.

Full-stack genomics pipelining with GATK4 + WDL + Cromwell

Kate Voss

GATK is a widely used variant calling toolkit from Broad that is now open source as of GATK4. Yay. WDL describes workflows using a DSL. Cromwell is the workflow runner that uses WDL. GATK4 is 5x faster than GATK3 and incorporates Spark. Now publish best practice practices for somatic variations, and germline/somatic copy number changes. Broad sequencings 24Tb of data a day. Cromwell runs on Google Compute Engine and working on AWS + Alibaba.

ToolDog - generating tool descriptors from the ELIXIR tool registry

Kenzo-Hugo Hillion is a registry for finding tools which helps with visibility and discoverability. ToolDog uses a unique source of information in to generate things like EDAM and Galaxy datatypes. ToolDog inspects the source code using Docker generating a template for a tool description. It can use existing descriptions and annotate them. Great way to improve tools with descriptions.

BioThings SDK: a toolkit for building high-performance data APIs in biology

Chunlei Wu

BioThings SDK builds off BioThings talk yesterday, describing the API used for building on top of it. Backend of BioThings is a DataHub, API, then front end. Two ways to use BioThings SDK. First, turn a data file into a BioThings API people can use: parse into JSON, describe how to index, then serve out as JSON with Elasticsearch. Second, aggregate multiple data sources and keep them up to date: parse multiple inputs, use MongoDB for staging.

Integrating cloud storage providers for genomic analyses

Ted Liefeld

GenomeSpace makes computational analyses integrated by connecting tools and data. 20 different tools integrated and multiple places to store files: S3, Dropbox, Google Drive, SwiftStack. Moves data around between different locations. Provides a FileSystemInterface Java SDK to access custom providers if want to use a non-provided storage solution. Provide a REST-ful API for retrieval.

Fighting Superbugs with Open Source Software

Kai Blin

Superbugs are drug resistant microbes, shows depressing and scary pictures of rate of drug resistance across European countries. These occur because of continued misuse of antibiotics. Use bacterial natural products which produce useful antibiotics and are very hard to synthesize. Nice to see some chemical structures. Idea: can we use genomes to identify these natural products. Open source software to do this: anitSMASH.