Clarify diff between 'hyphal growth' and 'filamentous growth'

[dianeoinglis]

There is an issue with the use of the two terms, GO:0030448 'hyphal growth' and GO:0030448 ''filamentous growth' and the use by curators that I am compelled to comment on. It's a use of terminology in disparate fields of fungal research.

First, growth as hyphae is a form of filamentous growth, however, the definition has made use of these terms as equivalents does not follow their use in the literature.

For strictly filamentous fungi, hyphal growth is the only option. The use of the term 'hyphal growth' is common in strictly filamentous species and it refers to the maintance of proper cell polarity in the growth of hyphae. When cell polarity during hyphal growth is disrupted, the hyphae still grow as hyphae (yeast form is not an option for strictly filamentous fungi) but, the normal polarized growth at the hyphal tips is abnormal. There may be bulbous cells and hyphae with bulges but they are still hyphae be they abnormal hyphal. So hyphal growth does not refer to the ability to grow as hyphae. It refers to hyphae that maintain the proper polarized growth pattern to form normal hyphae.

In contrast, Dimorphic fungi and C. albicans can grow either as proper yeast indistinguishable from true yeast and can convert to growth in the filamentous form that appears indistinguishable from strictly filamentous fungi. It is the inability to convert from a yeast form cell-type to the filamentous form that prompts curators to use the term 'filamentous growth.' Candida albicans researchers are guilty of using both terms, hyphal and growth, hyphae and filaments or mycelial growth to refer to the ability to grow as hyphal filaments. The ability to convert from a yeast-form cell to a filamentous-form is a different process than hyphae maintaining proper hyphal polarity but the terms have been applied interchangeable as researchers of dimorphic fungi use both terms and pretty much ignore the different use of the term 'hyphal growth' in strictly filamentous species such as Neurospora crassa.

The term definitions do not accurately reflect these different uses in literature and these different processes are annotated with identical terms, especially by Candida curators. Bad!

It would help greatly if these two term definitions more accurately reflected the proper use of these terms and pointed curators of Dimorphic species away from the use of

[dianeoinglis]

...away from the interchangeable use of the two terms for Candida albicans and other Dimorphs.

Can we please do something to clarify and improve this messy situation? I would be ever-so-happy!

Diane

[krchristie]

Hi Diane,

I am certainly open to clarification, though we'll need to get input from SGD (@srengel) as well. @mah11 might have useful comments as well.

Currently I see this basic structure in the ontology (some terms omitted):

- filamentous growth (GO:0030447)
-- filamentous growth of a population of unicellular organisms (GO:0044182)
--- growth of unicellular organism as a thread of attached cells (GO:0070783)
---- invasive filamentous growth (GO:0036267)
---- pseudohyphal growth (GO:0007124)
--- filamentous growth of a population of unicellular organisms in response to biotic stimulus (GO:0036180)
--- filamentous growth of a population of unicellular organisms in response to chemical stimulus (GO:0036171)
--- filamentous growth of a population of unicellular organisms in response to heat (GO:0036168)
--- filamentous growth of a population of unicellular organisms in response to pH (GO:0036177)
--- filamentous growth of a population of unicellular organisms in response to starvation (GO:0036170)
-- filamentous growth of a multicellular organism (GO:0044181) [0 annotations in AmiGO]
-- filamentous growth of a unicellular organism (GO:0044180) [0 annotations in AmiGO]
-- hyphal growth (GO:0030448)

Use of "filamentous growth" for annotation? Seeing that "filamentous growth" is the parent of "hyphal growth", a possible ontology solution might be to mark "filamentous growth" as part of the "do not manually annotate" set to force people to think about what organism they are annotating and which more specific term(s) are relevant.

That might help SGD too as I notice in YeastMine that there are direct annotations to "filamentous growth". My recollection of cerevisiae is that true hyphal growth isn't possible, so it seems it should be possible to annotate more specifically for cerevisiae genes, at least to "growth of unicellular organism as a thread of attached cells (GO:0070783)" if not to pseudohyphal growth for all annotations.

Do fungal annotators think that there is a situation where you would really want to be able to annotate directly to "filamentous growth" (or to the "regulation of filamentous growth" terms), or do you think that you should always be able to pick a more specific term? If there are fungi that can do both hyphal and pseudohyphal growth, this probably isn't an option.

Utility of these two terms? Also, I notice that neither of these two terms: -- filamentous growth of a multicellular organism (GO:0044181) [0 annotations in AmiGO] -- filamentous growth of a unicellular organism (GO:0044180) [0 annotations in AmiGO] has any annotations in AmiGO, though both are indicated as having been created in 2009 with this tag: GOC:mtg_cambridge_2009. If these terms have not been used in 8 years, perhaps they should be obsoleted. I have no idea what either refer to, or what would be the difference between "filamentous growth of a unicellular organism" and "filamentous growth of a population of unicellular organisms".

Need for both of these terms? Looking at the definitions of these two terms, invasive filamentous growth and pseudohyphal growth, I am wondering why we need invasive filamentous growth separately from pseudohyphal growth, when pseudohyphal growth also specifies invasion into the growth substrate.

• invasive filamentous growth (GO:0036267) Def: The growth of colonies in filamentous chains of cells into a substrate. creation_date: 2012-07-02T01:42:24Z

• pseudohyphal growth (GO:0007124) Def: A pattern of cell growth that occurs in conditions of nitrogen limitation and abundant fermentable carbon source. Cells become elongated, switch to a unipolar budding pattern, remain physically attached to each other, and invade the growth substrate. no creation date, so probably before 2009

[dianeoinglis]

Candida albicans can do both, true hyphal and pdeudohyphal growth and the processes are separable so terms for both can be applied together or independently, as appropriate. Let's not touch that.

I did the project at CGD that used and expanded the GO:0044182 to GO:0070783 and all the "in response to..." terms and it was published (PMID:23143685) so it would be preferable if that more granular branch of terms continued to be used. It seems like a good idea to note "do not annotated to" on the parent GO:0030447 'filamentous growth.'

The real issue I want to get at is the inappropriate use of the term 'hyphal growth' GO:0030448. I think it should not be used simply because authors interchangeably use filamentous growth and hyphal growth for the ability to grow as hyphae because other fungal research communities use the abbreviated "hyphal growth" to refer to proper polarization of growth in species that only make hyphae. I will open a new ticket and propose to obsolete 'hyphal growth' and propose a new, more appropriate and accurate term to reduce it's misuse. Perhaps a note on the definitions for "filamentous growth" terms can state that both true hyphae and pseudohyphae are considered filamentous growth forms.

This is an another aside: invasive growth occurs in S. cerevisiae haploid cells under nitrogen starvation. Only diploid S. cerevisiae grow pseudohyphally which is also invasive. There is some partial but not complete redundancy. It might be preferable for SGD to use a term like 'invasive growth' for the "haploid invasive growth" process and avoid direct annotations that include the term "filamentous" though it may still be a parent or ancestor.

Cc @smah11 Cc @sengel

[krchristie]

Before you open a new ticket, let's please continue the discussion on the appropriate fate/redefinition of the term "hyphal growth" in this ticket.

The other issues I brought up are because I used to annotate in the area of pseudohyphal growth and found the current structure quite confusing, so I think these are worth fixing while in this area.

[mah11]

I don't think I can add anything useful here - although I did work on some of the existing terms, it was many years ago and not from a position of first-hand expertise.

[dianeoinglis]

Ok. As I understand it, the mission of GO is unification of biology and this is a particular challenge with fungi. Curators are supposed to annotate to the BP reported, not necessarily to the favorite terms selected by authors. This is not quite what has happened or is happening and that is part of the problems​. The terms "hyphal growth" and "filamentous growth" are used inappropriately and/or imprecisicely to mean the same thing by some Candida albicans researchers. PMID:22496666 is a good example of a paper with horrible misuse of the term "hyphal growth'" along with "filament-inducing conditions" that if we're done as described in Spider medium at 37 deg would not necessarily produce cells in the true hyphal form but lead the unknowing reader to believe it does! The authors do correctly use a common and problematic buzzword "morphogenesis" that can be discussed separately as other terms are affected by this concept.

We have a very accurate term 'cell growth mode switching, budding to filamentous' GO: 0036187 that is actually what most of the filamentous' growth phenotypes affect in species capable of budding yeast and filamentous' forms of growth. I think a note directing curators to consider that term would be useful when there is a complete block in switching. The set of terms under 'filamentous growth of a population of unicellular organisms' are best used when filamentous' growth is affected in some but not all conditions, so the block in the switch is not absolute. This is typical of Candida albicans and was the impetus for creating the '...in response to" child terms.

I do not think the term 'hyphal growth' can be saved by refining the definition. It has already been used incorrectly. We also have to bring Marek Skrzypek at CGD into this discussion as he is the lone curator at CGD that will bear the impact of a change to the 248 direct annotations. I will email him directly with this issue# as I don't think he has a GitHub account.

The other misusage of the term "hyphal growth" creates an even worse problem. Historically, hyphal growth in strictly filamentous fungal species, such as Aspergillus nidulans and Neurospora crassa discuss hyphal growth in those species as "properly polarized and branched, linear hyphal" as opposed to bulging, meandering, more or less branched, abnormally shaped hyphae. Hyphal growth is the only option for Aspergillus and Neurospora and authors use the same term "hyphal growth," to refer to a totally different process, not the ability to grow as hyohae as is used in a dimorphic species like Candida albicans. See PMID:8969518 for an example of an A. nidulans paper that states "hyphal growth was slightly reduced" when hyphal growth is the only option for this species.

I will contact Marek asap and get his feedback at this point.

[jimhu-tamu]

Don't forget the bacteria! Streptomyces grows hyphae. Many others grow as filaments that are not considered hyphae, e.g. some cyanobacteria (Anabaena)

What's the differentia for hyphae vs filaments?

[krchristie]

Thanks for the comment @jimhu-tamu, I didn't know about bacterial hyphae at all, so I'm really glad you brought this up.

For fungi, hyphae are a specific type of filament where the cells develop into an extremely elongated tubular form that no longer has clear cellular divisions and, if I remember correctly, is multinucleate (@dianeoinglis probably has the details more clearly in her head, but you probably get the gist from this). This is in contrast to what is called pseudohyphae, where the cells are elongaged, but still clearly cellular with single nuclei, but the cells remain attached to each other and thus grow as a filament. Thus, in fungi, there are at least two types of filamentous growth: hyphal and pseudohyphal that are distinguished by the structure of the filament.

[ValWood]

2 points:

1. Form the closed ticket #17477 filamentous appears to include population growth i.e group of organisms (out of scope for GO?) in addition to cell level filamentous growth.

The existing definitions need to address exactly what we mean by this as a "growth" process. Researchers refer to filamentous growth but sometimes they are usually describing a "growth of a population" (out of scope for GO) and sometimes "cell/ and or population morphology" which occurs as part of a lifestyle stage (in scope).

2. ~@krchristie In response to your question above: GO:0030448 hyphal growth Definition Growth of fungi as threadlike, tubular structures that may contain multiple nuclei and may or may not be divided internally by septa, or cross-walls. so if this is correct the multinucleate /multiseptate nature is not a sufficient differentia because it may or may not need to be present (unless this definition is incorrect). The key appears to be in Diane's comment "When cell polarity during hyphal growth is disrupted, the hyphae still grow as hyphae (yeast form is not an option for strictly filamentous fungi) but, the normal polarized growth at the hyphal tips is abnormal."~ ignore this part ,I don't think this is correct

i.e hyphal growth for fungi that grow constitutively as hyphae pseudohyphal growth for fungi with a yeast-form lifestyle stage

@CuzickA could you check this difference with Kim H-K?

[krchristie]

Form the closed ticket #17477 filamentous appears to include population growth i.e group of organisms (out of scope for GO?) in addition to cell level filamentous growth.

The existing definitions need to address exactly what we mean by this as a "growth" process. Researchers refer to filamentous growth but sometimes they are usually describing a "growth of a population" (out of scope for GO) and sometimes "cell/ and or population morphology" which occurs as part of a lifestyle stage (in scope).

I'm not really keen to deal with the reference to 'populations' as these terms were put in with a lot of input from CGD.

@krchristie In response to your question above: GO:0030448 hyphal growth Definition Growth of fungi as threadlike, tubular structures that may contain multiple nuclei and may or may not be divided internally by septa, or cross-walls.

so if this is correct the multinucleate /multiseptate nature is not a sufficient differentia because it may or may not need to be present (unless this definition is incorrect).

The key appears to be in Diane's comment "When cell polarity during hyphal growth is disrupted, the hyphae still grow as hyphae (yeast form is not an option for strictly filamentous fungi) but, the normal polarized growth at the hyphal tips is abnormal."

i.e hyphal growth for fungi that grow constitutively as hyphae pseudohyphal growth for fungi with a yeast-form lifestyle stage

I'm not sure to which question you were referring. However, the fact that the definition states that they hyphae "may or may not be divided internally by septa, or cross-walls." has no applicability to pseudohyphae. Pseudohyphae are composed of distinct cells, while fungal hyphae are multinucleate tubes that may or may not periodically include a septum.

However, the fact that @jimhu-tamu says that bacteria have hyphae indicates that there is a problem, in that this definition is specific to fungal hyphae.

[krchristie]

Here is the definition of the term hyphal growth: Def: Growth of fungi as threadlike, tubular structures that may contain multiple nuclei and may or may not be divided internally by septa, or cross-walls.

Despite specifying "fungi", this term has been used for annotation of the bacterium Streptomyces coelicolor.

From https://en.wikipedia.org/wiki/Hypha, it seems that oomycetes can also grow as hyphae:

A hypha (plural hyphae, from Greek ὑφή, huphḗ, "web") is a long, branching filamentous structure of a fungus, oomycete, or actinobacterium.[1] In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium.

A hypha consists of one or more cells surrounded by a tubular cell wall.

[krchristie]

Similarly to some of the fungi, Streptomyces bacteria seem to only grow in hyphal forms. However, there is a transition from vegetative hyphae, the vegetative growth state, to aerial hyphae, which develop into spores in response to nutrient depletion.

Bobek J, Šmídová K, Čihák M. A Waking Review: Old and Novel Insights into the Spore Germination in Streptomyces. Front Microbiol. 2017 Nov 13;8:2205. doi: 10.3389/fmicb.2017.02205. eCollection 2017. Review. PMID:29180988

The life cycle of Streptomyces, similarly as in the other arthrospore-forming bacteria, encompasses a development of a network of branched hyphae that grow into the substrate thus creating a vegetative mycelium. The subsequent development of aerial hyphae and spores is considered to be the cell’s response to nutrient depletion.

[krchristie]

Hyphal growth in Streptomyces seems to share similarity with what @dianeoinglis said about strictly filamentous fungi:

The use of the term 'hyphal growth' is common in strictly filamentous species and it refers to the maintance of proper cell polarity in the growth of hyphae.

Flärdh K. Cell polarity and the control of apical growth in Streptomyces. Curr Opin Microbiol. 2010 Dec;13(6):758-65. doi: 10.1016/j.mib.2010.10.002. Review. PMID:21036658.

Growth of Streptomyces obligately depends on pronounced cell polarity. These Gram-positives of the phylum Actinobacteria grow as hyphae that build their cell walls at hyphal tips [1, 2, 3]. All tips are created by spore germination or lateral branching; the latter involving selection of a site along the hyphal side, marking it with a molecular landmark, and recruiting and organising the machinery for cell wall growth at this site, thereby establishing a new polarity axis. This polarisation is repeated over and over during Streptomyces growth and is independent of cell division, which is in sharp contrast to most other examples of bacterial cell polarity that depend on recognition of one or both of the cell poles that are generated by division [4].

[ValWood]

In this case this ticket does not address my concerns, so I'll reopen the ticket that I opened yesterday and clarify.

[ValWood]

My comments from the redundant ticket: I'm trying to establish with certaintly how hyphal growth differs from filamentous growth. It has become clear that they are different from the discussions in the other ticket. However the definitions do not make this distinction clear.

SInce hyphal growth is a type of filamentous growth, following a genus differentia hyphal growth should be defined

A type of filamentous growth that "add differentia here"

Currently the differentia appears to be: that may contain multiple nuclei and may or may not be divided internally by septa, or cross-walls.

but because the definition says "may or may not contain these differentia" I am struggling to figure out what exactly is different from the parent term? There must be some defining criteria that is always present?

[ValWood]

In addition, it isn't really clear what we mean by "growth" in this context.

The papers I looked at describing hyphal growth are describing "colony morphology" (this fungus can grow in filamentous/hyphal form. This refers to a population and is really about proliferation (growth plus division). This seems to be out of scope for GO. Note that in GO we only represent an expansion of specific cell-types in GO, not organismal proliferation (population expansion).

When the term "hyphal growth" is used to refer to specific hyphae (-which is within scope for GO), "hyphal growth" refers to "growth + morphology" not just to growth. For example, misshapen hyphae would be classed as a problem with hyphal growth. This might be OK, I am never sure. I think I questioned this once and @mah11 said it was OK because growth also has a direction (but this seems to be lacking from the definition of growth?)

[ValWood]

I looked at the first two publications for hyphal growth annotation in QuickGO

so for example, the first candida paper annotation

http://europepmc.org/abstract/MED/19154328 deletion of the Ca2+ transporters that modulate cytosolic [Ca2+] (Mid1, Cch1 or Pmr1) did not affect hyphal length but curve formation was severely reduced in mid1Delta and cch1Delta and abolished in pmr1Delta.

this is referring to hyphal morphology, not to a size increase.

Some with the second paper annotating HAC1 to "hyphal growth" http://europepmc.org/abstract/MED/18602013 In addition, we show that Hac1 plays an important role in regulating the morphology of C. albicans and in the expression of genes encoding cell surface proteins during ER stress, factors that are important in virulence of this fungal pathogen.

again, this is about morphology, not growth.

So I'm not really sure what we are trying to capture with the "hyphal growth" annotations....

[mah11]

I think I questioned this once and @mah11 said it was OK because growth also has a direction ...

The only relevant thing I recall is in the discussion of "regulation of cell growth" and its subtypes (see #15463), where, yes, regulation of growth direction is a way to regulate growth. It seems the same would hold for hyphal growth and its regulation. Beyond that I don't think I know enough to help.

[ValWood]

Yeah, don't worry I was just gathering the info from the other ticket. I might be able to make a suggestion here shortly from PHI-Base work. @CuzickA and I have been discussing hyphal growth recently.

[srengel]

tagging @marekskrzypek

[marekskrzypek]

In Candida albicans there is more than just morphology in "hyphal growth". Yeast-like cells and hyphae not only look different, they also express distinct sets of genes and have elaborate regulatory systems for the purpose of switching between those two forms and maintaining them in response to external stimuli. So, this is more like a developmental program, not just an expansion of cell populations.

[ValWood]

at present these "growth stages" are defined as "The increase in size or mass of an entire organism, a part of an organism or a cell"

They terms describe an increase in cell size. This isn't what the curation is trying to describe. However, the curation is a mixed bag because the word 'growth ' is used in different contexts to describe size increases, life cycle growth phases, and aspects of morphology, and sometimes population growth (viability). It's going to be tricky to pull all of these apart, and reannotation will be required.

[ValWood]

see also https://github.com/geneontology/go-ontology/issues/18465