Bloom Lab Profile picture
Lab studying molecular evolution of proteins and viruses. Affiliated with @fredhutch @HHMINEWS @uwgenome. @jbloomlab@bsky
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Mar 5 11 tweets 4 min read
Over 4 yrs after being first to publicly release SARS-CoV-2 genome, Yong-Zhen Zhang just published large set of viral seqs from first stage of COVID-19 outbreak in China


He uses data to suggest scenarios re early outbreak & root of viral phylogenetic tree academic.oup.com/ve/advance-art…
Image Zhang recruited nearly all COVID-19 patients hospitalized at Shanghai Public Health Center in first 2/3 (Jan-Sep) of 2020.

The largest source of Shanghai patients in Jan/Feb 2020 was imported cases from Wuhan or elsewhere in Hubei, thereby providing window into Wuhan outbreak. Image
Feb 7 18 tweets 7 min read
In new study led by Caleb Carr & @khdcrawford, we measure how all mutation to Lassa virus glycoprotein complex (GPC) affect cell entry & antibody escape

Results show how prospective assessment of effects of mutations can inform design of countermeasures
biorxiv.org/content/10.110… As background, Lassa virus causes of thousands of deaths each year, mostly from spillovers from its rodent host, but there is occasional human-to-human transmission.

Lassa is biosafety-level-4 priority pathogen, & efforts are underway to develop vaccines & antibody therapeutics.
Jan 17 4 tweets 2 min read
Here is my brief analysis of Dec-28-2019 SARSCoV2 submission to Genbank.

This analysis supports my conclusion to WSJ () that this submission does not tell origin of virus, but does show sequence known to Chinese Academy of Sciences weeks before released wsj.com/politics/natio…
Image Here is link to my full analysis:

See also images of the same posted below (although it's probably just easier to click on link above and read HTML). github.com/jbloom/SARS2_2…



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Dec 17, 2023 11 tweets 3 min read
In new study led by Frances Welsh, we map how mutations to influenza affect neutralization by antibodies from humans of various ages

We find differences in mutation effects among age groups

Virus has evolved especially to escape antibodies of teenagers

biorxiv.org/content/10.110… As background, human influenza constantly evolving. So people exposed to different strains, depending on their age & idiosyncratic history of infection/vaccination.

Different exposure histories cause people to make antibodies w different specificities

rupress.org/jem/article/21…
Nov 29, 2023 15 tweets 5 min read
I wanted to highlight this pre-print by David Ho’s group on the neutralizing antibody response to new (XBB.1.5-based) COVID vaccine booster, as it illustrates some points related to paradigm of updating SARS-CoV-2 vaccines to keep pace w viral evolution.
biorxiv.org/content/10.110… Recall original COVID vaccines worked very well against early SARS-CoV-2 strains

Unfortunately, virus has been evolving, so antibodies elicited by that vaccine don’t neutralize newer viral variants very well

(Other human CoVs also evolve same way: ) journals.plos.org/plospathogens/…
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Nov 15, 2023 20 tweets 7 min read
In study led by @bdadonaite we measure how mutations to XBB.1.5 spike affect cell entry, ACE2 binding & serum escape

Two key findings

1⃣ Mutations outside RBD meaningfully affect ACE2 binding

2⃣ Measurements help predict viral clade growth in real worldbiorxiv.org/content/10.110… We made spike pseudovirus deep mutational scanning libraries of mutations across XBB.1.5 spike (as well as XBB.1.5 RBD and BA.2 spike libraries).

We used these libraries to measure how >9,000 mutations affected cell entry, ACE2 binding, and serum antibody escape. Image
Nov 3, 2023 7 tweets 4 min read
In new work led by Will Hannon, we have created tool for visualizing deep mutational scanning data on protein structures, such as to aid in understanding effects of viral mutations.

Tool is at

Pre-print describing tool: dms-viz.github.io
biorxiv.org/content/10.110… Tool makes it easy to visualize mutation-level measurements for a protein in context of structure. In this thread, I will walk through some examples.
Sep 28, 2023 5 tweets 2 min read
There have been many experimental papers on BA.2.86 over last month. This one by David Ho's group is one of most comprehensive:

I'm going to quickly summarize key points for people having hard time keeping up w all the recent BA.2.86 papers.biorxiv.org/content/10.110… 1⃣ Serum neutralization of BA.2.86 roughly comparable to XBB.1.5, & comparable or slightly better than newer XBB variants like EG.5.1

Similar results (within few-fold) reported by other groups too, eg @yunlong_cao @BenjMurrell @BarouchLab @sigallab @ShanLuLiu1 @SystemsVirology
Aug 30, 2023 10 tweets 4 min read
Here are data from new XBB.1.5 spike deep mutational scanning by @bdadonaite in our group

Go to see how mutations affect:

1⃣ Neutralization by human XBB breakthrough sera

2⃣ Spike-mediated pseudovirus entry in 293T-ACE2 cells

3⃣ Spike affinity for ACE2dms-vep.github.io/SARS-CoV-2_XBB… It will be a few weeks before we finish & post pre-print for study, but we wanted to share data now for those interested in interpreting current SARS2 evolution.

Measurements were made using lentiviral deep mutational scanning () with XBB.1.5 spike.sciencedirect.com/science/articl…
Aug 16, 2023 12 tweets 5 min read
I wanted to provide assessment of spike amino-acid mutations in new highly mutated 2nd generation BA.2 SARS-CoV-2 variant

This is analysis for those (like me) scientifically interested in SARS2 evolution

(Anyone else is completely within reason to ignore this variant right now) Full analysis of the mutations is in these slides:

Analysis is based mostly on deep mutational scanning experiments

TLDR: lots of antigenic change, and some interesting RBD mutations (addition of N-linked glycan & deletion in receptor-binding motif)slides.com/jbloom/new_2nd…
Aug 3, 2023 12 tweets 3 min read
In new study, we develop rigorous method to jointly analyze deep mutational scanning of different protein homologs or conditions

We use it to identify mutations w effects on spike-mediated viral entry that differ by >1,000-fold among #SARSCoV2 strains.

biorxiv.org/content/10.110… As background, common question in evolution is if some mutations have different effects in different homologs or conditions

Eg, our lab has measured how most mutations to Delta, BA.1 & BA.2 spike affect viral entry. Which mutations have different effects in these viral variants?
Jul 27, 2023 15 tweets 5 min read
This paper from Linfa Wang’s group to which @tylernstarr & I contributed illustrates interesting points about

1⃣ Importance of imprinting for antibody specificity to SARS-like CoV

2⃣ How it may be easier to broadly neutralize animal sarbecoviruses than human #SARSCoV2 variants Briefly, the study (which was led by Wan Ni Chia @CheeWahTan2 @LokShee @linfa_wang), isolated antibodies from person who had been infected by SARS-CoV-1 in ~2003, then received Pfizer SARS-CoV-2 vaccine in 2021.
Jul 6, 2023 4 tweets 2 min read
A few brief thoughts on antigenic impact of F456L mutation that is becoming more common in #SARSCoV2 XBB strains.

@yunlong_cao et al *already* measured impact of this mutation on human serum antibody neutralization in their recent preprint, and it causes ~1.5-fold titer drop. Specifically, see Extended Data Fig 6 of

Spike of XBB.1.5.10 is XBB.1.5 + F456L, so compare those strains to see effect of F456L.

Across three cohorts, F456L causes titer drops of:

207 -> 148 (1.4-fold)

251 -> 178 (1.4-fold)

562 -> 379 (1.5-fold) biorxiv.org/content/10.110…
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Jun 5, 2023 6 tweets 4 min read
I wanted to post notes on potentially beneficial non-spike mutations in #SARSCoV2 variants XBB.1.16 & XBB.1.9.1, two of fastest growing variants.

These are from estimates of effects of mutations to all SARS-CoV-2 proteins from @richardneher & myself Both XBB.1.16 & XBB.1.9.1 have I5T mutation in ORF9b innate-immune antagonist accessory protein. XBB.1.16 also has N55S in this protein.

According to our estimates (jbloomlab.github.io/SARS2-mut-fitn…), I5T in ORF9b is beneficial while N55S is roughly neutral Image
May 16, 2023 21 tweets 8 min read
I’ve created new SARS-CoV-2 antibody escape calculator () with latest data from @yunlong_cao

TLDR: look at image below for likely future sites of antigenic evolution in XBB spike.

For details, read full thread below. https://t.co/yB43xtDIuLjbloomlab.github.io/SARS2-RBD-esca…
Image Escape calculator uses deep mutational scanning to quantify antibody escape caused by mutations.

Update is based on large new dataset recently posted by @yunlong_cao et al:

Dataset is first to include antibodies induced by multiple Omicron infections.
Apr 27, 2023 57 tweets 19 min read
In new study, I have analyzed correlation between SARS-CoV-2 & animal genetic material in full set of environmental samples from Huanan Seafood Market.


Analysis clarifies what sequencing these samples can & cannot tell us about early outbreak at market.biorxiv.org/content/10.110… Background:

China first reported coronavirus cases associated w market & no human transmission. But then we learned was human transmission & some early cases not from market.

Thus began still unanswered questions of role of market, nicely summarized here science.org/content/articl…
Apr 13, 2023 4 tweets 2 min read
I wanted to flag this study by Lihong Liu, David Ho, et al that identifies new class of #SARSCoV2 antibodies that neutralize all major variants from early strains (eg, D614G) to current strains (eg, XBB.1.5): biorxiv.org/content/10.110… These antibodies, 12-16 and 12-19, bind to an epitope at the interface of the NTD and SD-1 domain.

They block ACE2 binding, but not by directly binding the RBD.

Instead, they lock the RBD in the down conformation, as schematized below. Image
Apr 11, 2023 4 tweets 4 min read
The final version of our study on how the SARS-CoV-2 mutational spectrum has shifted during the virus's evolution is published in @MolBioEvol: academic.oup.com/mbe/advance-ar…

This was a collaboration with Annabel Beichmann, @richardneher, and @Kelley__Harris Below is the summary of the study from when we posted the pre-print:

The main addition in the final version is that we have expanded to more viruses the analysis of the mutational spectrum versus equilibrium nucleotide frequencies.
Mar 25, 2023 18 tweets 8 min read
In a new study led by @CaelanRadford in collaboration with @FKlein_lab, we use an improved deep mutational scanning system to map the neutralizing specificities of broad human polyclonal serum antibodies from individuals living with HIV.
biorxiv.org/content/10.110… As background, HIV infection sometimes elicits antibodies that broadly neutralize many strains.

Individual broadly neutralizing antibodies have been extensively characterized, but it is much harder to map the neutralizing specificity of the actual polyclonal antibody response.
Mar 22, 2023 28 tweets 8 min read
I’ve refrained from commenting on metagenomics of environmental samples from Huanan Seafood Market, since media coverage preceded description of data or analysis.

Data still not available, but there is now enough written down to offer partially informed assessment. TLDR is I agree w WHO’s @DrTedros ():

These data don’t tell us how pandemic began, but every bit of information helps.

Here is what I glean from the available analyses by the two groups w access.
Mar 16, 2023 8 tweets 4 min read
Minor update to our previously described work estimating fitness effects of amino-acid mutations to all SARS-CoV-2 proteins ():

We have added estimates for the ORF9b accessory protein, which is encoded in overlapping reading frame in N gene. SARS-CoV-2 trackers (eg, @SolidEvidence @siamosolocani @dfocosi) speculate ORF9b mutations maybe relevant in recent variants ( & )

I'm not sufficiently informed on ORF9b to offer opinion on whether they are correct.