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Immune Profiling: Standardizing and Accessing Immunogenetic Data

Deep sequencing of antibody/B-cell and T-cell receptor repertoires (AIRR-Seq Data) can help understand the dynamics of immune repertoire in vaccinology,…

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8 months ago

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Recent advances in sequencing technology have made it possible to sample the immune repertoire in exquisite detail. Deep sequencing of antibody/B-cell and T-cell receptor repertoires (AIRR-seq data) has enormous promise for understanding the dynamics of the immune repertoire in vaccinology, infectious diseases, autoimmunity, and cancer biology, but also poses significant challenges. “The data are very complicated, there are many steps to obtaining them, and each of those steps can be done slightly differently,” said Felix Breden, PhD, co-founder of the Adaptive Immune Receptor Repertoire (AIRR) Community and scientific director of iReceptor.

Felix Breden
Felix Breden, PhD, is co-founder of the Adaptive Immune Receptor Repertoire (AIRR) Community and scientific director of iReceptor.

According to Breden, genes of the adaptive immune system are some of the most complicated, duplicated, and highly evolved genes in vertebrates. “Trying to understand the immunoglobulin and T-cell receptor loci and the expression of the T-cell and B-cell repertoires require data standardization to facilitate sharing. But the process of implementing standardization is slow, takes community initiative, face-to-face work, and follow-up.”

This need led Jamie Scott, PhD, Tom Kepler, PhD, and Breden to brainstorm an Open Science grassroots community in 2014. Today, the AIRR Community is an official committee of The Antibody Society and develops and promotes standards and recommendations for obtaining, analyzing, curating, and comparing/sharing AIRR-seq datasets.1 They validate tools to analyze AIRR-seq data and relate AIRR-seq datasets to other “big data” sets, such as microarray, flow cytometric, MiSeq, and single-cell gene-expression data, and address the legal and ethical issues involving the use and sharing of datasets derived from human sources.

The AIRR Community developed the AIRR Data Commons, which follow a distributed data model and is currently composed of seven globally distributed repositories that provide public access to more than 80 MiARR-compliant studies, including many COVID-19 studies, and the accompanying AIRR-seq data.2 MiARR is a set of standards and protocols for curating and sharing the immense repositories.

The focus of the iReceptor platform is to federate the large AIRR Data Commons and to facilitate the curation, analysis, and sharing of these antibody/B-cell and T-cell receptor repertoires. The platform connects the distributed network, allowing queries across multiple projects, labs, and institutions. Over five billion sequences and 8,987 repertoires are currently available from seven remote repositories, 70 research labs, and 85 studies.

Single Cell Immune Profiling_Breden1
The iReceptor platform federates the large AIRR Data Commons and facilitates the curation, analysis, and sharing of these antibody/B-cell and T-cell receptor repertoires. [Felix Brendan]
“Think of the AIRR Data Commons as a beautiful art gallery where you can show your data, in a usable form, to the world, and the iReceptor Gateway as the Google of AIRR repertoires, enabling queries such as ‘federate all repertoires of ovarian cancer patients under a particular treatment.’ Studies produce huge amounts of data from only a few samples, and, sometimes, the signal is very weak and difficult to use for predictions. There is a real need is to bring the data together from multiple studies to get larger sample sizes,” said Breden.

Present functionalities allow searching for repertoires satisfying certain metadata, repertoires that contain specific CDR3 sequences, and identified repertoires for sequences derived from particular V, D, and J genes and alleles. Sequences can be downloaded in AIRR.tsv format, easily importable to other AIRR-seq analysis tools, or analyzed through the Gateway with common tools.

Important new functionalities of the AIRR Data Commons and the iReceptor Gateway are the ability to curate, share, and analyze single-cell profiling data. This approach allows linkage of an immune receptor with the physiological state of the cell. “It is a huge advantage in trying to understand and predict the behavior of the adaptive immune system,” said Breden.

“Since single-cell sample sizes are smaller, sharing becomes even more important. The AIRR Data Commons are AIRR-seq data repositories from multiple laboratories that anyone can use,” said Breden. Located at Simon Fraser University, the iReceptor Gateway, an implementation of the vision of the AIRR Community, follows the AIRR Community standards and is part of the EU/CIHR funded iReceptor Plus Consortium.3

Single-cell immune profiling is only going to get more complicated and the data more difficult to curate. “Community-adopted standards are increasingly important,” said Breden. “The AIRR Community is open and transparent. We publish papers with standards we have developed and then distribute them to be voted on by the entire community to get buy-in. Anyone can actively become involved in a Working Group.”

To query or contribute to the AIRR Data Commons contact support@ iReceptor.org.

Single Cell Immune Profiling_Breden2
New functionalities of the AIRR Data Commons and the iReceptor Gateway are the ability to curate, share, and analyze single-cell profiling data. [Felix Brendan]
References

  1. Trück J, Eugster A, Barennes P, Tipton CM, Luning Prak ET, et al. Biological controls for standardization and interpretation of adaptive immune receptor repertoire profiling (2021) eLife;10:e66274.
  2. Christley S, Aguiar A, Blanck G, Breden F, Bukhari SAC, et al. The ADC API: A web API for the programmatic query of the AIRR Data Commons. (2020) Big Data; 3:22.
  3. Corrie BD, Marthandan N, Zimonja B, Jaglale J, Zhou Z, et al. iReceptor: a platform for querying and analyzing antibody/B-cell and T-cell receptor repertoire data across federated repositories. (2018) Immunol Rev.; 284(1): 24–41.

The post Immune Profiling: Standardizing and Accessing Immunogenetic Data appeared first on GEN - Genetic Engineering and Biotechnology News.

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Fighting the Surveillance State Begins with the Individual

It’s a well-known fact at this point that in the United States and most of the so-called free countries that there is a robust surveillance state in…

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21 hours ago

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October 23, 2023

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It’s a well-known fact at this point that in the United States and most of the so-called free countries that there is a robust surveillance state in place, collecting data on the entire populace. This has been proven beyond a shadow of a doubt by people like Edward Snowden, a National Security Agency (NSA) whistleblower who exposed that the NSA was conducting mass surveillance on US citizens and the world as a whole. The NSA used applications like those from Prism Systems to piggyback on corporations and the data collection their users had agreed to in the terms of service. Google would scan all emails sent to a Gmail address to use for personalized advertising. The government then went to these companies and demanded the data, and this is what makes the surveillance state so interesting. Neo-Marxists like Shoshana Zuboff have dubbed this “surveillance capitalism.” In China, the mass surveillance is conducted at a loss. Setting up closed-circuit television cameras and hiring government workers to be a mandatory editorial staff for blogs and social media can get quite expensive. But if you parasitically leech off a profitable business practice it means that the surveillance state will turn a profit, which is a great asset and an even greater weakness for the system. You see, when that is what your surveillance state is predicated on you’ve effectively given your subjects an opt-out button. They stop using services that spy on them. There is software and online services that are called “open source,” which refers to software whose code is publicly available and can be viewed by anyone so that you can see exactly what that software does. The opposite of this, and what you’re likely already familiar with, is proprietary software. Open-source software generally markets itself as privacy respecting and doesn’t participate in data collection. Services like that can really undo the tricky situation we’ve found ourselves in. It’s a simple fact of life that when the government is given a power—whether that be to regulate, surveil, tax, or plunder—it is nigh impossible to wrestle it away from the state outside somehow disposing of the state entirely. This is why the issue of undoing mass surveillance is of the utmost importance. If the government has the power to spy on its populace, it will. There are people, like the creators of The Social Dilemma, who think that the solution to these privacy invasions isn’t less government but more government, arguing that data collection should be taxed to dissuade the practice or that regulation needs to be put into place to actively prevent abuses. This is silly to anyone who understands the effect regulations have and how the internet really works. You see, data collection is necessary. You can’t have email without some elements of data collection because it’s simply how the protocol functions. The issue is how that data is stored and used. A tax on data collection itself will simply become another cost of doing business. A large company like Google can afford to pay a tax. But a company like Proton Mail, a smaller, more privacy-respecting business, likely couldn’t. Proton Mail’s business model is based on paid subscriptions. If there were additional taxes imposed on them, it’s possible that they would not be able to afford the cost and would be forced out of the market. To reiterate, if one really cares about the destruction of the surveillance state, the first step is to personally make changes to how you interact with online services and to whom you choose to give your data.

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Stock Market Today: Stocks turn higher as Treasury yields retreat; big tech earnings up next

A pullback in Treasury yields has stocks moving higher Monday heading into a busy earnings week and a key 2-year bond auction later on Tuesday.

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21 hours ago

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October 23, 2023

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Updated at 11:52 am EDT U.S. stocks turned higher Monday, heading into the busiest earnings week of the year on Wall Street, amid a pullback in Treasury bond yields that followed the first breach of 5% for 10-year notes since 2007. Investors, however, continue to track developments in Israel's war with Hamas, which launched its deadly attack from Gaza three weeks ago, as leaders around the region, and the wider world, work to contain the fighting and broker at least a form of cease-fire. Humanitarian aid is also making its way into Gaza, through the territory's border with Egypt, as officials continue to work for the release of more than 200 Israelis taken hostage by Hamas during the October 7 attack. Those diplomatic efforts eased some of the market's concern in overnight trading, but the lingering risk that regional adversaries such as Iran, or even Saudi Arabia, could be drawn into the conflict continues to blunt risk appetite. Still, the U.S. dollar index, which tracks the greenback against a basket of six global currencies and acts as the safe-haven benchmark in times of market turmoil, fell 0.37% in early New York trading 105.773, suggesting some modest moves into riskier assets. The Japanese yen, however, eased past the 150 mark in overnight dealing, a level that has some traders awaiting intervention from the Bank of Japan and which may have triggered small amounts of dollar sales and yen purchases. In the bond market, benchmark 10-year note yields breached the 5% mark in overnight trading, after briefly surpassing that level late last week for the first time since 2007, but were last seen trading at 4.867% ahead of $141 billion in 2-year, 5-year and 7-year note auctions later this week. Global oil prices were also lower, following two consecutive weekly gains that has take Brent crude, the global pricing benchmark, firmly past $90 a barrel amid supply disruption concerns tied to the middle east conflict. Brent contracts for December delivery were last seen $1.06 lower on the session at $91.07 per barrel while WTI futures contract for the same month fell $1.36 to $86.72 per barrel. Market volatility gauges were also active, with the CBOE Group's VIX index hitting a fresh seven-month high of $23.08 before easing to $20.18 later in the session. That level suggests traders are expecting ranges on the S&P 500 of around 1.26%, or 53 points, over the next month. A busy earnings week also indicates the likelihood of elevated trading volatility, with 158 S&P 500 companies reporting third quarter earnings over the next five days, including mega cap tech names such as Google parent Alphabet  (GOOGL) - Get Free Report, Microsoft  (MSFT) - Get Free Report, retail and cloud computing giant Amazon  (AMZN) - Get Free Report and Facebook owner Meta Platforms  (META) - Get Free Report. "It’s shaping up to be a big week for the market and it comes as the S&P 500 is testing a key level—the four-month low it set earlier this month," said Chris Larkin, managing director for trading and investing at E*TRADE from Morgan Stanley. "How the market responds to that test may hinge on sentiment, which often plays a larger-than-average role around this time of year," he added. "And right now, concerns about rising interest rates and geopolitical turmoil have the potential to exacerbate the market’s swings." Heading into the middle of the trading day on Wall Street, the S&P 500, which is down 8% from its early July peak, the highest of the year, was up 10 points, or 0.25%. The Dow Jones Industrial Average, which slumped into negative territory for the year last week, was marked 10 points lower while the Nasdaq, which fell 4.31% last week, was up 66 points, or 0.51%. In overseas markets, Europe's Stoxx 600 was marked 0.11% lower by the close of Frankfurt trading, with markets largely tracking U.S. stocks as well as the broader conflict in Israel. In Asia, a  slump in China stocks took the benchmark CSI 300 to a fresh 2019 low and pulled the region-wide MSCI ex-Japan 0.72% lower into the close of trading.
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iPhone Maker Foxconn Investigated By Chinese Authorities

Foxconn, the Taiwanese company that manufactures iPhones on behalf of Apple (AAPL), is being investigated by Chinese authorities, according to multiple…

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23 hours ago

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October 23, 2023

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Foxconn, the Taiwanese company that manufactures iPhones on behalf of Apple (AAPL), is being investigated by Chinese authorities, according to multiple media reports. Foxconn’s business has been searched by Chinese authorities and China’s main tax authority has conducted inspections of Foxconn’s manufacturing operations in the Chinese provinces of Guangdong and Jiangsu. At the same time, China’s natural-resources department has begun onsite investigations into Foxconn’s land use in Henan and Hubei provinces within China. Foxconn has manufacturing facilities focused on Apple products in three of the Chinese provinces where authorities are carrying out searches. While headquartered in Taiwan, Foxconn has a huge manufacturing presence in China and is a large employer in the nation of 1.4 billion people. The investigations suggest that China is ramping up pressure on the company as Foxconn considers major investments in India, and as presidential elections approach in Taiwan. Foxconn founder Terry Gou said in August of this year that he intends to run for the Taiwanese presidency. He has resigned from the company’s board of directors but continues to hold a 12.5% stake in the company. Gou is currently in fourth place in the polls ahead of the election that is scheduled to be held in January 2024. The potential impact on Apple and its iPhone manufacturing comes amid rising political tensions between politicians in Washington, D.C. and Beijing. Apple’s stock has risen 16% over the last 12 months and currently trades at $172.88 U.S. per share.  

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